Molecules

24 pages, 2446 KiB

Open AccessArticle

Molecular Dynamics Simulation of Kir6.2 Variants Reveals Potential Association with Diabetes Mellitus

by Mohamed E. Elangeeb, Imadeldin Elfaki, Ali M. S. Eleragi, Elsadig Mohamed Ahmed, Rashid Mir, Salem M. Alzahrani, Ruqaiah I. Bedaiwi, Zeyad M. Alharbi, Mohammad Muzaffar Mir, Mohammad Rehan Ajmal, Faris Jamal Tayeb and Jameel Barnawi

Molecules 2024, 29(8), 1904; https://doi.org/10.3390/molecules29081904 - 22 Apr 2024

Viewed by 406

Abstract

Diabetes mellitus (DM) represents a problem for the healthcare system worldwide. DM has very serious complications such as blindness, kidney failure, and cardiovascular disease. In addition to the very bad socioeconomic impacts, it influences patients and their families and communities. The global costs [...] Read more.

Diabetes mellitus (DM) represents a problem for the healthcare system worldwide. DM has very serious complications such as blindness, kidney failure, and cardiovascular disease. In addition to the very bad socioeconomic impacts, it influences patients and their families and communities. The global costs of DM and its complications are huge and expected to rise by the year 2030. DM is caused by genetic and environmental risk factors. Genetic testing will aid in early diagnosis and identification of susceptible individuals or populations using ATP-sensitive potassium (K_ATP) channels present in different tissues such as the pancreas, myocardium, myocytes, and nervous tissues. The channels respond to different concentrations of blood sugar, stimulation by hormones, or ischemic conditions. In pancreatic cells, they regulate the secretion of insulin and glucagon. Mutations in the KCNJ11 gene that encodes the Kir6.2 protein (a major constituent of K_ATP channels) were reported to be associated with Type 2 DM, neonatal diabetes mellitus (NDM), and maturity-onset diabetes of the young (MODY). Kir6.2 harbors binding sites for ATP and phosphatidylinositol 4,5-diphosphate (PIP2). The ATP inhibits the K_ATP channel, while the (PIP2) activates it. A Kir6.2 mutation at tyrosine330 (Y330) was demonstrated to reduce ATP inhibition and predisposes to NDM. In this study, we examined the effect of mutations on the Kir6.2 structure using bioinformatics tools and molecular dynamic simulations (SIFT, PolyPhen, SNAP2, PANTHER, PhD&SNP, SNP&Go, I-Mutant, MuPro, MutPred, ConSurf, HOPE, and GROMACS). Our results indicated that M199R, R201H, R206H, and Y330H mutations influence Kir6.2 structure and function and therefore may cause DM. We conclude that MD simulations are useful techniques to predict the effects of mutations on protein structure. In addition, the M199R, R201H, R206H, and Y330H variant in the Kir6.2 protein may be associated with DM. These results require further verification in protein–protein interactions, Kir6.2 function, and case-control studies. Full article

(This article belongs to the Special Issue Molecular Dynamics Simulations of Biomacromolecules)

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17 pages, 2690 KiB

Open AccessArticle

Synthesis, Spectroscopic Properties, and Metalation of 3-Alkoxybenziporphyrins

by Rachel A. Tomlovich and Timothy D. Lash

Molecules 2024, 29(8), 1903; https://doi.org/10.3390/molecules29081903 - 22 Apr 2024

Viewed by 304

Abstract

A series of 5-alkoxy-1,3-benzenedicarbaldehydes and related dimers were prepared in three steps from dimethyl 5-hydroxyisophthalate. Acid catalyzed condensation of the dialdehydes with a tripyrrane dicarboxylic acid, followed by oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, afforded good yields of 3-alkoxybenziporphyrins, although dimeric tetraaldehydes failed to give isolatable [...] Read more.

A series of 5-alkoxy-1,3-benzenedicarbaldehydes and related dimers were prepared in three steps from dimethyl 5-hydroxyisophthalate. Acid catalyzed condensation of the dialdehydes with a tripyrrane dicarboxylic acid, followed by oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, afforded good yields of 3-alkoxybenziporphyrins, although dimeric tetraaldehydes failed to give isolatable porphyrinoid products. Proton NMR spectroscopy gave no indication of an aromatic ring current, but addition of trifluoroacetic acid resulted in the formation of dications that exhibited weakly diatropic characteristics. Spectroscopic titration with TFA demonstrated that stepwise protonation took place, generating monocationic and dicationic species. 3-Alkoxybenziporphyrins reacted with nickel(II) or palladium(II) acetate to give the related nickel(II) or palladium(II) complexes. These stable organometallic derivatives showed increased diatropic properties that were most pronounced for the palladium(II) complexes. These unique porphyrinoids provide further insights into the properties of benziporphyrins. Full article

(This article belongs to the Special Issue Porphyrin-Based Compounds: Synthesis and Application, 2nd Edition)

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14 pages, 2757 KiB

Open AccessArticle

Room Temperature Diels–Alder Reactions of 4-Vinylimidazoles

by Brandon B. Fulton, Alexia J. Hartzell, H. V. Rasika Dias and Carl J. Lovely

Molecules 2024, 29(8), 1902; https://doi.org/10.3390/molecules29081902 - 22 Apr 2024

Viewed by 318

Abstract

In the course of studying Diels–Alder reactions of 4-vinylimidazoles with N-phenylmaleimide, it was discovered that they engage in cycloaddition at room temperature to give high yields of the initial cycloadduct as a single stereoisomer. In certain cases, the product precipitated out of [...] Read more.

In the course of studying Diels–Alder reactions of 4-vinylimidazoles with N-phenylmaleimide, it was discovered that they engage in cycloaddition at room temperature to give high yields of the initial cycloadduct as a single stereoisomer. In certain cases, the product precipitated out of the reaction mixture and could be isolated by simple filtration, thereby avoiding issues with aromatization observed during chromatographic purification. Given these results, intramolecular variants using doubly activated dienophiles were also investigated at room temperature. Amides underwent cycloaddition at room temperature in modest yields, but the initial adducts were not isolable with N_imid-benzyl-protected systems. Attempts to extend these results to the corresponding esters and hydroxamate were less successful with these substrates only undergoing cycloaddition at elevated temperatures in lower yields. Density functional theory calculations were performed to evaluate the putative transition states for both the inter- and intramolecular variants to rationalize experimental observations. Full article

(This article belongs to the Special Issue Advances in Synthesis and Biological Activity of Novel Derivatives Based on Five-Membered Heterocyclic Scaffolds and Their Intermediates—Second Edition)

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17 pages, 10731 KiB

Open AccessArticle

Anti-Tumor Activity and Mechanism of Silibinin Based on Network Pharmacology and Experimental Verification

by Peihai Li, Dexu Wang, Xueliang Yang, Changyu Liu, Xiaobin Li, Xuanming Zhang, Kechun Liu, Yun Zhang, Mengqi Zhang, Changyun Wang and Rongchun Wang

Molecules 2024, 29(8), 1901; https://doi.org/10.3390/molecules29081901 - 22 Apr 2024

Viewed by 408

Abstract

Silibinin is a flavonoid compound extracted from the seeds of Silybum marianum (L.) Gaertn. It has the functions of liver protection, blood-lipid reduction and anti-tumor effects. However, the potential molecular mechanism of silibinin against tumors is still unknown. This study aimed to assess [...] Read more.

Silibinin is a flavonoid compound extracted from the seeds of Silybum marianum (L.) Gaertn. It has the functions of liver protection, blood-lipid reduction and anti-tumor effects. However, the potential molecular mechanism of silibinin against tumors is still unknown. This study aimed to assess the anti-tumor effects of silibinin in adenoid cystic carcinoma (ACC2) cells and Balb/c nude mice, and explore its potential mechanism based on network pharmacology prediction and experimental verification. A total of 347 targets interacting with silibinin were collected, and 75 targets related to the tumor growth process for silibinin were filtrated. Based on the PPI analysis, CASP3, SRC, ESR1, JAK2, PRKACA, HSPA8 and CAT showed stronger interactions with other factors and may be the key targets of silibinin for treating tumors. The predicted target proteins according to network pharmacology were verified using Western blot analysis in ACC2 cells and Balb/c nude mice. In the pharmacological experiment, silibinin was revealed to significantly inhibit viability, proliferation, migration and induce the apoptosis of ACC2 cells in vitro, as well as inhibit the growth and development of tumor tissue in vivo. Western blot analysis showed that silibinin affected the expression of proteins associated with cell proliferation, migration and apoptosis, such as MMP3, JNK, PPARα and JAK. The possible molecular mechanism involved in cancer pathways, PI3K-Akt signaling pathway and viral carcinogenesis pathway via the inhibition of CASP3, MMP3, SRC, MAPK10 and CDK6 and the activation of PPARα and JAK. Overall, our results provided insight into the pharmacological mechanisms of silibinin in the treatment of tumors. These results offer a support for the anti-tumor uses of silibinin. Full article

(This article belongs to the Special Issue Medicinal Value of Natural Bioactive Compounds and Plant Extracts II)

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69 pages, 1736 KiB

Open AccessSystematic Review

The Ocean’s Pharmacy: Health Discoveries in Marine Algae

by Mélanie Silva, Dorit Avni, João Varela and Luísa Barreira

Molecules 2024, 29(8), 1900; https://doi.org/10.3390/molecules29081900 - 22 Apr 2024

Viewed by 384

Abstract

Non-communicable diseases (NCDs) represent a global health challenge, constituting a major cause of mortality and disease burden in the 21st century. Addressing the prevention and management of NCDs is crucial for improving global public health, emphasizing the need for comprehensive strategies, early interventions, [...] Read more.

Non-communicable diseases (NCDs) represent a global health challenge, constituting a major cause of mortality and disease burden in the 21st century. Addressing the prevention and management of NCDs is crucial for improving global public health, emphasizing the need for comprehensive strategies, early interventions, and innovative therapeutic approaches to mitigate their far-reaching consequences. Marine organisms, mainly algae, produce diverse marine natural products with significant therapeutic potential. Harnessing the largely untapped potential of algae could revolutionize drug development and contribute to combating NCDs, marking a crucial step toward natural and targeted therapeutic approaches. This review examines bioactive extracts, compounds, and commercial products derived from macro- and microalgae, exploring their protective properties against oxidative stress, inflammation, cardiovascular, gastrointestinal, metabolic diseases, and cancer across in vitro, cell-based, in vivo, and clinical studies. Most research focuses on macroalgae, demonstrating antioxidant, anti-inflammatory, cardioprotective, gut health modulation, metabolic health promotion, and anti-cancer effects. Microalgae products also exhibit anti-inflammatory, cardioprotective, and anti-cancer properties. Although studies mainly investigated extracts and fractions, isolated compounds from algae have also been explored. Notably, polysaccharides, phlorotannins, carotenoids, and terpenes emerge as prominent compounds, collectively representing 42.4% of the investigated compounds. Full article

(This article belongs to the Special Issue Marine Natural Products: A Hidden Wealth and a New Epoch for Drug Development)

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12 pages, 4558 KiB

Open AccessArticle

Construction of TiO₂/CuPc Heterojunctions for the Efficient Photocatalytic Reduction of CO₂ with Water

by Jun Wang, Shuang Fu, Peng Hou, Jun Liu, Chao Li, Hongguang Zhang and Guowei Wang

Molecules 2024, 29(8), 1899; https://doi.org/10.3390/molecules29081899 - 22 Apr 2024

Viewed by 293

Abstract

Utilizing solar energy for photocatalytic CO₂ reduction is an attractive research field because of its convenience, safety, and practicality. The selection of an appropriate photocatalyst is the key to achieve efficient CO₂ reduction. Herein, we report the synthesis of TiO₂ [...] Read more.

Utilizing solar energy for photocatalytic CO₂ reduction is an attractive research field because of its convenience, safety, and practicality. The selection of an appropriate photocatalyst is the key to achieve efficient CO₂ reduction. Herein, we report the synthesis of TiO₂/CuPc heterojunctions by compositing CuPc with TiO₂ microspheres via a hydroxyl-induced self-assembly process. The experimental investigations demonstrated that the optimal TiO₂/0.5CuPc photocatalyst exhibited a significantly enhanced CO₂ photoreduction rate up to 32.4 μmol·g⁻¹·h⁻¹ under 300 W xenon lamp irradiation, which was 3.7 times that of the TiO₂ microspheres alone. The results of photoelectrochemical experiments indicated that the construction of the heterojunctions by introducing CuPc effectively promoted the separation and transport of photogenerated carriers, thus enhancing the catalytic effect of the photocatalyst. Full article

(This article belongs to the Special Issue Photocatalytic Materials and Photocatalytic Reactions)

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13 pages, 5338 KiB

Open AccessArticle

Development of Glycosylation-Modified ^DPPA-1 Compounds as Innovative PD-1/PD-L1 Blockers: Design, Synthesis, and Biological Evaluation

by Peng Deng, Xiaodan Dong, Ziyuan Wu, Xixi Hou, Longfei Mao, Jingjing Guo, Wenshan Zhao, Chune Peng, Zhe Zhang and Lizeng Peng

Molecules 2024, 29(8), 1898; https://doi.org/10.3390/molecules29081898 - 22 Apr 2024

Viewed by 351

Abstract

In the context of peptide drug development, glycosylation plays a pivotal role. Accordingly, L-type peptides were synthesized predicated upon the PD-1/PD-L1 blocker ^DPPA-1. Subsequent glycosylation resulted in the production of two distinct glycopeptides, D-glu-^LPPA-1 and D-gal-^LPPA-1, by using [...] Read more.

In the context of peptide drug development, glycosylation plays a pivotal role. Accordingly, L-type peptides were synthesized predicated upon the PD-1/PD-L1 blocker ^DPPA-1. Subsequent glycosylation resulted in the production of two distinct glycopeptides, D-glu-^LPPA-1 and D-gal-^LPPA-1, by using D-glucose (D-glu) and D-galactose (D-gal), respectively, during glycosylation. Both glycopeptides significantly inhibited the interaction between PD-1 and PD-L1, and the measured half maximal inhibitory concentrations (IC_50s) were 75.5 μM and 101.9 μM for D-glu-LPPA-1 and D-gal-LPPA-1, respectively. Furthermore, D-gal-LPPA-1 displayed a pronounced ability to restore T-cell functionality. In an MC38 tumor-bearing mouse model, D-gal-LPPA-1 demonstrated a significant inhibitory effect. Notably, D-gal-LPPA-1 substantially augmented the abundance and functionality of CD8⁺ T cells in the tumor microenvironment. Additionally, in the lymph nodes and spleens, D-gal-LPPA-1 significantly increased the proportion of CD8⁺ T cells secreting interferon-gamma (IFN-γ). These strong findings position D-gal-LPPA-1 as a potent enhancer of the antitumor immune response in MC38 tumor-bearing mice, underscoring its potential as a formidable PD-1/PD-L1 blocking agent. Full article

(This article belongs to the Section Medicinal Chemistry)

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15 pages, 3012 KiB

Open AccessArticle

Beneficial Effects of Dietary Fiber in Young Barley Leaf on Gut Microbiota and Immunity in Mice

by Seita Chudan, Takuto Kurakawa, Miyu Nishikawa, Yoshinori Nagai, Yoshiaki Tabuchi, Shinichi Ikushiro and Yukihiro Furusawa

Molecules 2024, 29(8), 1897; https://doi.org/10.3390/molecules29081897 - 22 Apr 2024

Viewed by 306

Abstract

The health benefits of young barley leaves, rich in dietary fiber, have been studied for several decades; however, their beneficial effects on the intestinal microenvironment remain to be elucidated. To investigate the effects of young barley leaf-derived dietary fiber (YB) on the gut [...] Read more.

The health benefits of young barley leaves, rich in dietary fiber, have been studied for several decades; however, their beneficial effects on the intestinal microenvironment remain to be elucidated. To investigate the effects of young barley leaf-derived dietary fiber (YB) on the gut microbiota and immunity, mice were fed an AIN-93G diet containing cellulose or YB and subjected to subsequent analysis. The population of MHC-II-positive conventional dendritic cells (cDCs) and CD86 expression in the cDCs of Peyer’s patches were elevated in the YB-fed mice. MHC-II and CD86 expression was also elevated in the bone marrow-derived DCs treated with YB. 16S-based metagenomic analysis revealed that the gut microbiota composition was markedly altered by YB feeding. Among the gut microbiota, Lachnospiraceae, mainly comprising butyrate-producing NK4A136 spp., were overrepresented in the YB-fed mice. In fact, fecal butyrate concentration was also augmented in the YB-fed mice, which coincided with increased retinaldehyde dehydrogenase (RALDH) activity in the CD103⁺ cDCs of the mesenteric lymph nodes. Consistent with elevated RALDH activity, the population of colonic IgA⁺ plasma cells was higher in the YB-fed mice than in the parental control mice. In conclusion, YB has beneficial effects on the gut microbiota and intestinal immune system. Full article

(This article belongs to the Special Issue Natural Products and Microbiology in Human Health)

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18 pages, 1517 KiB

Open AccessReview

Predictive and Prognostic Biomarkers and Tumor Antigens for Targeted Therapy in Urothelial Carcinoma

by Aditya Eturi, Amman Bhasin, Kevin K. Zarrabi and William J. Tester

Molecules 2024, 29(8), 1896; https://doi.org/10.3390/molecules29081896 - 22 Apr 2024

Viewed by 348

Abstract

Urothelial carcinoma (UC) is the fourth most prevalent cancer amongst males worldwide. While patients with non-muscle-invasive disease have a favorable prognosis, 25% of UC patients present with locally advanced disease which is associated with a 10–15% 5-year survival rate and poor overall prognosis. [...] Read more.

Urothelial carcinoma (UC) is the fourth most prevalent cancer amongst males worldwide. While patients with non-muscle-invasive disease have a favorable prognosis, 25% of UC patients present with locally advanced disease which is associated with a 10–15% 5-year survival rate and poor overall prognosis. Muscle-invasive bladder cancer (MIBC) is associated with about 50% 5 year survival when treated by radical cystectomy or trimodality therapy; stage IV disease is associated with 10–15% 5 year survival. Current therapeutic modalities for MIBC include neoadjuvant chemotherapy, surgery and/or chemoradiation, although patients with relapsed or refractory disease have a poor prognosis. However, the rapid success of immuno-oncology in various hematologic and solid malignancies offers new targets with tremendous therapeutic potential in UC. Historically, there were no predictive biomarkers to guide the clinical management and treatment of UC, and biomarker development was an unmet need. However, recent and ongoing clinical trials have identified several promising tumor biomarkers that have the potential to serve as predictive or prognostic tools in UC. This review provides a comprehensive summary of emerging biomarkers and molecular tumor targets including programmed death ligand 1 (PD-L1), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), fibroblast growth factor receptor (FGFR), DNA damage response and repair (DDR) mutations, poly (ADP-ribose) polymerase (PARP) expression and circulating tumor DNA (ctDNA), as well as their clinical utility in UC. We also evaluate recent advancements in precision oncology in UC, while illustrating limiting factors and challenges related to the clinical application of these biomarkers in clinical practice. Full article

(This article belongs to the Special Issue Current Advances in the Discovery and Development of New Therapies against Cancer)

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15 pages, 3374 KiB

Open AccessArticle

Improving the Quality of Wheat Flour Bread by a Thermophilic Xylanase with Ultra Activity and Stability Reconstructed by Ancestral Sequence and Computational-Aided Analysis

by Guoshuai Hu, Xizhi Hong, Meixin Zhu, Lei Lei, Zhenggang Han, Yong Meng and Jiangke Yang

Molecules 2024, 29(8), 1895; https://doi.org/10.3390/molecules29081895 - 22 Apr 2024

Viewed by 286

Abstract

Xylanase is an essential component used to hydrolyze the xylan in wheat flour to enhance the quality of bread. Presently, cold-activated xylanase is popularly utilized to aid in the development of dough. In this study, ancestral sequence reconstruction and molecular docking of xylanase [...] Read more.

Xylanase is an essential component used to hydrolyze the xylan in wheat flour to enhance the quality of bread. Presently, cold-activated xylanase is popularly utilized to aid in the development of dough. In this study, ancestral sequence reconstruction and molecular docking of xylanase and wheat xylan were used to enhance the activity and stability of a thermophilic xylanase. The results indicated that the ancestral enzyme TmxN3 exhibited significantly improved activity and thermal stability. The Vmax increased by 2.7 times, and the catalytic efficiency (K_cat/K_m) increased by 1.7 times in comparison to TmxB. After being incubated at 100 °C for 120 min, it still retained 87.3% of its activity, and the half-life in 100 °C was 330 min, while the wild type xylanase was only 55 min. This resulted in an improved shelf life of bread, while adding TmxN3 considerably enhanced its quality with excellent volume and reduced hardness, chewiness, and gumminess. The results showed that the hardness was reduced by 55.2%, the chewiness was reduced by 40.11%, and the gumminess was reduced by 53.52%. To facilitate its industrial application, we further optimized the production conditions in a 5L bioreactor, and the xylanase activity reached 1.52 × 10⁶ U/mL culture. Full article

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13 pages, 5160 KiB

Open AccessArticle

Phosphorus Modification of Iron: Mechanistic Insights into Ammonia Synthesis on Fe₂P Catalyst

by Abdulrahman Almithn

Molecules 2024, 29(8), 1894; https://doi.org/10.3390/molecules29081894 - 22 Apr 2024

Viewed by 290

Abstract

Ammonia (NH₃) is a critical chemical for fertilizer production and a potential future energy carrier within a sustainable hydrogen economy. The industrial Haber–Bosch process, though effective, operates under harsh conditions due to the high thermodynamic stability of the nitrogen molecule (N [...] Read more.

Ammonia (NH₃) is a critical chemical for fertilizer production and a potential future energy carrier within a sustainable hydrogen economy. The industrial Haber–Bosch process, though effective, operates under harsh conditions due to the high thermodynamic stability of the nitrogen molecule (N₂). This motivates the search for alternative catalysts that facilitate ammonia synthesis at milder temperatures and pressures. Theoretical and experimental studies suggest that circumventing the trade-off between N–N activation and subsequent NH_x hydrogenation, governed by the Brønsted–Evans–Polanyi (BEP) relationship, is key to achieving this goal. Recent studies indicate metal phosphides as promising catalyst materials. In this work, a comprehensive density functional theory (DFT) study comparing the mechanisms and potential reaction pathways for ammonia synthesis on Fe(110) and Fe₂P(001) is presented. The results reveal substantial differences in the adsorption strengths of NH_x intermediates, with Fe₂P(001) exhibiting weaker binding compared to Fe(110). For N–N bond cleavage, multiple competing pathways become viable on Fe₂P(001), including routes involving the pre-hydrogenation of adsorbed N₂ (e.g., through *NNH*). Analysis of DFT-derived turnover rates as a function of hydrogen pressure (H₂) highlights the increased importance of these hydrogenated intermediates on Fe₂P(001) compared to Fe(110) where direct N₂ dissociation dominates. These findings suggest that phosphorus incorporation modifies the ammonia synthesis mechanism, offering alternative pathways that may circumvent the limitations of traditional transition metal catalysts. This work provides theoretical insights for the rational design of Fe-based catalysts and motivates further exploration of phosphide-based materials for sustainable ammonia production. Full article

(This article belongs to the Special Issue New Metal Catalysts for Sustainable Chemistry)

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16 pages, 11298 KiB

Open AccessArticle

Based on HPLC and HS-GC-IMS Techniques, the Changes in the Internal Chemical Components of Schisandra chinensis (Turcz.) Baill. Fruit at Different Harvesting Periods Were Analyzed

by Bowei Sun, Yiping Yan, Mingjie Ma, Jinli Wen, Yanli He, Yining Sun, Pengqiang Yuan, Peilei Xu, Yiming Yang, Zihao Zhao, Li Cao and Wenpeng Lu

Molecules 2024, 29(8), 1893; https://doi.org/10.3390/molecules29081893 - 22 Apr 2024

Viewed by 402

Abstract

Schisandra chinensis, as a traditional Chinese herbal medicine, has clear pharmacological effects such as treating asthma, protecting nerves and blood vessels, and having anti-inflammatory properties. Although the Schisandra chinensis fruit contain multiple active components, the lignans have been widely studied as the [...] Read more.

Schisandra chinensis, as a traditional Chinese herbal medicine, has clear pharmacological effects such as treating asthma, protecting nerves and blood vessels, and having anti-inflammatory properties. Although the Schisandra chinensis fruit contain multiple active components, the lignans have been widely studied as the primary pharmacologically active compound. The volatile chemical components of Schisandra chinensis include a large amount of terpenes, which have been proven to have broad pharmacological activities. However, when to harvest to ensure the highest accumulation of pharmacologically active components in Schisandra chinensis fruits is a critical issue. The Schisandra chinensis fruit trees in the resource nursery were all planted in 2019 and began bearing fruit in 2021. Their nutritional status and tree vigor remain consistently good. The content of lignans and organic acids in the fruits of Schisandra chinensis over seven different harvest periods was tested, and the results of high-performance liquid chromatography (HPLC) indicated that the lignan content was higher, at 35 mg/g, in late July, and the organic acid content was higher, at 72.34 mg/g, in early September. If lignans and organic acids are to be selected as raw materials for pharmacological development, the harvest can be carried out at this stage. Using HS-GC-IMS technology, a total of 67 volatile flavor substances were detected, and the fingerprint of the volatile flavor substances in the different picking periods was established. It was shown by the results that the content of volatile flavor substances was the highest in early August, and 16 flavor substances were selected by odor activity value (OAV). The variable importance in projection (VIP) values of 16 substances were further screened, and terpinolene was identified as the key volatile flavor substance that caused the aroma characteristics of Schisandra chinensis fruit at different harvesting periods. If the aroma component content of Schisandra chinensis fruit is planned to be used as raw material for development and utilization, then early August, when the aroma component content is higher, should be chosen as the time for harvest. This study provides a theoretical basis for the suitable harvesting time of Schisandra chinensis for different uses, and promotes the high-quality development of the Schisandra chinensis industry. Full article

(This article belongs to the Special Issue Analysis of Phytochemical Components II)

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2 pages, 345 KiB

Open AccessCorrection

Correction: Miranda et al. Anion Binding by Fluorescent Ureido-Hexahomotrioxacalix[3]arene Receptors: An NMR, Absorption and Emission Spectroscopic Study. Molecules 2022, 27, 3247

by Alexandre S. Miranda, Paula M. Marcos, José R. Ascenso, Mário N. Berberan-Santos and Filipe Menezes

Molecules 2024, 29(8), 1892; https://doi.org/10.3390/molecules29081892 - 22 Apr 2024

Viewed by 179

Abstract

In the original publication [...] Full article

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14 pages, 2491 KiB

Open AccessArticle

Effects of Red Sorghum-Derived Deoxyanthocyanidins and Their O-β-D-Glucosides on E-Cadherin Promoter Activity in PC-3 Prostate Cancer Cells

by Nathalie Mora, Maxence Rosa, Mohamed Touaibia and Luc J. Martin

Molecules 2024, 29(8), 1891; https://doi.org/10.3390/molecules29081891 - 21 Apr 2024

Viewed by 477

Abstract

Although much less common than anthocyanins, 3-Deoxyanthocyanidins (3-DAs) and their glucosides can be found in cereals such as red sorghum. It is speculated that their bioavailability is higher than that of anthocyanins. Thus far, little is known regarding the therapeutic effects of 3-DAs [...] Read more.

Although much less common than anthocyanins, 3-Deoxyanthocyanidins (3-DAs) and their glucosides can be found in cereals such as red sorghum. It is speculated that their bioavailability is higher than that of anthocyanins. Thus far, little is known regarding the therapeutic effects of 3-DAs and their O-β-D-glucosides on cancer, including prostate cancer. Thus, we evaluated their potential to decrease cell viability, to modulate the activity of transcription factors such as NFκB, CREB, and SOX, and to regulate the expression of the gene CDH1, encoding E-Cadherin. We found that 4′,7-dihydroxyflavylium chloride (P7) and the natural apigeninidin can reduce cell viability, whereas 4′,7-dihydroxyflavylium chloride (P7) and 4′-hydroxy-7-O-β-D-glucopyranosyloxyflavylium chloride (P3) increase the activities of NFkB, CREB, and SOX transcription factors, leading to the upregulation of CDH1 promoter activity in PC-3 prostate cancer cells. Thus, these compounds may contribute to the inhibition of the epithelial-to-mesenchymal transition in cancer cells and prevent the metastatic activity of more aggressive forms of androgen-resistant prostate cancer. Full article

(This article belongs to the Special Issue Metabolites of Biofunctional Interest from Plant Sources)

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14 pages, 2507 KiB

Open AccessArticle

Carbon Dots Anchoring Single-Atom Pt on C₃N₄ Boosting Photocatalytic Hydrogen Evolution

by Jing Wang, Jiayu Song, Xin Kang, Dongxu Wang, Chungui Tian, Qin Zhang, Hui Zhao and Jiancong Liu

Molecules 2024, 29(8), 1890; https://doi.org/10.3390/molecules29081890 - 21 Apr 2024

Viewed by 397

Abstract

Carbon nitride (C₃N₄) has gained considerable attention and has been regarded as an ideal candidate for photocatalytic hydrogen evolution. However, its photocatalytic efficiency is still unsatisfactory due to the rapid recombination rate of photo-generated carriers and restricted surface area [...] Read more.

Carbon nitride (C₃N₄) has gained considerable attention and has been regarded as an ideal candidate for photocatalytic hydrogen evolution. However, its photocatalytic efficiency is still unsatisfactory due to the rapid recombination rate of photo-generated carriers and restricted surface area with few active sites. Herein, we successfully synthesized a single-atom Pt cocatalyst-loaded photocatalyst by utilizing the anchoring effect of carbon dots (CDs) on C₃N₄. The introduction of CDs onto the porous C₃N₄ matrix can greatly enhance the specific surface area of C₃N₄ to provide more surface-active sites, increase light absorption capabilities, as well as improve the charge separation efficiency. Notably, the functional groups of CDs can efficiently anchor the single-atom Pt, thus improving the atomic utilization efficiency of Pt cocatalysts. A strong interaction is formed via the connection of Pt-N bonds, which enhances the efficiency of photogenerated electron separation. This unique structure remarkably improves its H₂ evolution performance under visible light irradiation with a rate of 15.09 mmol h⁻¹ g⁻¹. This work provides a new approach to constructing efficient photocatalysts by using CDs for sustainable hydrogen generation, offering a practical approach to utilizing solar energy for clean fuel production. Full article

(This article belongs to the Special Issue Feature Papers in Applied Chemistry: 3rd Edition)

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18 pages, 4982 KiB

Open AccessArticle

An Optimized Method for Evaluating the Preparation of High-Quality Fuel from Various Types of Biomass through Torrefaction

by Shuai Guo, Xiaoyan Deng, Deng Zhao, Shujun Zhu, Hongwei Qu, Xingcan Li and Yan Zhao

Molecules 2024, 29(8), 1889; https://doi.org/10.3390/molecules29081889 - 21 Apr 2024

Viewed by 429

Abstract

The pretreatment for torrefaction impacts the performance of biomass fuels and operational costs. Given their diversity, it is crucial to determine the optimal torrefaction conditions for different types of biomass. In this study, three typical solid biofuels, corn stover (CS), agaric fungus bran [...] Read more.

The pretreatment for torrefaction impacts the performance of biomass fuels and operational costs. Given their diversity, it is crucial to determine the optimal torrefaction conditions for different types of biomass. In this study, three typical solid biofuels, corn stover (CS), agaric fungus bran (AFB), and spent coffee grounds (SCGs), were prepared using fluidized bed torrefaction. The thermal stability of different fuels was extensively discussed and a novel comprehensive fuel index, “displacement level”, was analyzed. The functional groups, pore structures, and microstructural differences between the three raw materials and the optimally torrefied biochar were thoroughly characterized. Finally, the biomass fuel consumption for household heating and water supply was calculated. The results showed that the optimal torrefaction temperatures for CS, AFB, and SCGs were 240, 280, and 280 °C, respectively, with comprehensive quality rankings of the optimal torrefied biochar of AFB (260) > SCG (252) > CS (248). Additionally, the economic costs of the optimally torrefied biochar were reduced by 7.03–19.32%. The results indicated that the displacement level is an index universally applicable to the preparation of solid fuels through biomass torrefaction. AFB is the most suitable solid fuel to be upgraded through torrefaction and has the potential to replace coal. Full article

(This article belongs to the Special Issue Renewable Energy, Fuels and Chemicals from Biomass)

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16 pages, 5054 KiB

Open AccessArticle

Dragon’s Blood-Loaded Mesoporous Silica Nanoparticles for Rapid Hemostasis and Antibacterial Activity

by Cuiyun Yin, Yihang Li, Jing Yu, Zhaoyou Deng, Shifang Liu, Xuanchao Shi, Deying Tang, Xi Chen and Lixia Zhang

Molecules 2024, 29(8), 1888; https://doi.org/10.3390/molecules29081888 - 21 Apr 2024

Viewed by 415

Abstract

Dragon’s blood (DB) is a traditional Chinese medicine (TCM) with hemostatic effects and antibacterial properties. However, it is still challenging to use for rapid hemostasis because of its insolubility. In this study, different amounts of DB were loaded on mesoporous silica nanoparticles (MSNs) [...] Read more.

Dragon’s blood (DB) is a traditional Chinese medicine (TCM) with hemostatic effects and antibacterial properties. However, it is still challenging to use for rapid hemostasis because of its insolubility. In this study, different amounts of DB were loaded on mesoporous silica nanoparticles (MSNs) to prepare a series of DB-MSN composites (5DB-MSN, 10DB-MSN, and 20DB-MSN). DB-MSN could quickly release DB and activate the intrinsic blood coagulation cascade simultaneously by DB and MSN. Hemostasis tests demonstrated that DB-MSN showed superior hemostatic effects than either DB or MSNs alone, and 10DB-MSN exhibited the best hemostatic effect. In addition, the antibacterial activities of DB-MSN against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) improved with the increase in DB. Furthermore, the hemolysis assay and cytocompatibility assay demonstrated that all DB-MSNs exhibited excellent biocompatibility. Based on these results, 10DB-MSN is expected to have potential applications for emergency hemostatic and antibacterial treatment in pre-hospital trauma. Full article

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20 pages, 5725 KiB

Open AccessArticle

One-Step Synthesis of Polyethyleneimine-Grafted Styrene-Maleic Anhydride Copolymer Adsorbents for Effective Adsorption of Anionic Dyes

by Yao Xu, Qinwen Wang, Yuanbo Wang, Falu Hu, Bin Sun, Tingting Gao and Guowei Zhou

Molecules 2024, 29(8), 1887; https://doi.org/10.3390/molecules29081887 - 21 Apr 2024

Viewed by 333

Abstract

Wastewater containing organic dyes has become one of the important challenges in water treatment due to its high salt content and resistance to natural degradation. In this work, a novelty adsorbent, PEI-SMA, was prepared by grafting polyethyleneimine (PEI) onto styrene-maleic anhydride copolymer (SMA) [...] Read more.

Wastewater containing organic dyes has become one of the important challenges in water treatment due to its high salt content and resistance to natural degradation. In this work, a novelty adsorbent, PEI-SMA, was prepared by grafting polyethyleneimine (PEI) onto styrene-maleic anhydride copolymer (SMA) through an amidation reaction. The various factors, such as pH, adsorbent dosage, contact time, dye concentration, and temperature, which may affect the adsorption of PEI-SMA for Reactive Black 5 (RB5), were systematically investigated by static adsorption experiments. The adsorption process of PEI-SMA for RB5 was more consistent with the Langmuir isotherm model and the pseudo-second-order model, suggesting a single-layer chemisorption. PEI-SMA exhibits excellent adsorption performance for RB5 dye, with a maximum adsorption capacity of 1749.19 mg g^–1 at pH = 2. Additionally, PEI-SMA exhibited highly efficient RB5 competitive adsorption against coexisting Cl⁻ and SO₄²⁻ ions and cationic dyes. The adsorption mechanism was explored, and it can be explained as the synergistic effect of electrostatic interaction, hydrogen bonding and π–π interaction. This study demonstrates that PEI-SMA could act as a high performance and promising candidate for the effective adsorption of anionic dyes from aqueous solutions. Full article

(This article belongs to the Collection Green Energy and Environmental Materials)

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15 pages, 6207 KiB

Open AccessArticle

Control of Optical Reflection in Ca₂MgWO₆ by Co and Mo Doping

by Kazuki Yamaguchi, Kohei Minagawa, Ryohei Oka and Toshiyuki Masui

Molecules 2024, 29(8), 1886; https://doi.org/10.3390/molecules29081886 - 21 Apr 2024

Viewed by 336

Abstract

To develop novel inorganic red pigments without harmful elements, we focused on the band structure of Ca₂(Mg, Co)WO₆ and attempted to narrow its bandgap by replacing the W⁶⁺ sites in the host structure of Mo⁶⁺. Ca₂ [...] Read more.

To develop novel inorganic red pigments without harmful elements, we focused on the band structure of Ca₂(Mg, Co)WO₆ and attempted to narrow its bandgap by replacing the W⁶⁺ sites in the host structure of Mo⁶⁺. Ca₂Mg_1−xCo_xW_1−yMo_yO₆ (0.10 ≤ x ≤ 0.30; 0.45 ≤ y ≤ 0.60) samples were synthesized by a sol-gel method using citric acids, and the crystal structure, optical properties, and color of the samples were characterized. The Ca₂Mg_1−xCo_xW_1−yMo_yO₆ solid solution was successfully formed, which absorbed visible light at wavelengths below 600 nm. In addition, the absorption wavelength shifted to longer wavelengths with increasing Mo⁶⁺ content. This is because a new conduction band composed of a Co_3d-W_5d-Mo_4d hybrid orbital was formed by Mo⁶⁺ doping to reduce the bandgap energy. Thus, the color of the samples gradually changed from pale orange to dark red, with a hue angle (h°) of less than 35°. Based on the above results, the optical absorption wavelength of the Ca₂Mg_1−xCo_xW_1−yMo_yO₆ system can be controlled to change the color by adjusting the bandgap energy. Full article

(This article belongs to the Section Colorants)

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21 pages, 10887 KiB

Open AccessArticle

Design of Na₃MnZr(PO₄)₃/Carbon Nanofiber Free-Standing Cathodes for Sodium-Ion Batteries with Enhanced Electrochemical Performances through Different Electrospinning Approaches

by Debora Maria Conti, Claudia Urru, Giovanna Bruni, Pietro Galinetto, Benedetta Albini, Chiara Milanese, Silvia Pisani, Vittorio Berbenni and Doretta Capsoni

Molecules 2024, 29(8), 1885; https://doi.org/10.3390/molecules29081885 - 20 Apr 2024

Viewed by 460

Abstract

The NASICON-structured Na₃MnZr(PO₄)₃ compound is a promising high-voltage cathode material for sodium-ion batteries (SIBs). In this study, an easy and scalable electrospinning approach was used to synthesize self-standing cathodes based on Na₃MnZr(PO₄)₃ loaded [...] Read more.

The NASICON-structured Na₃MnZr(PO₄)₃ compound is a promising high-voltage cathode material for sodium-ion batteries (SIBs). In this study, an easy and scalable electrospinning approach was used to synthesize self-standing cathodes based on Na₃MnZr(PO₄)₃ loaded into carbon nanofibers (CNFs). Different strategies were applied to load the active material. All the employed characterization techniques (X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS), thermal gravimetric analysis (TGA), and Raman spectroscopy) confirmed the successful loading. Compared to an appositely prepared tape-cast electrode, Na₃MnZr(PO₄)₃/CNF self-standing cathodes demonstrated an enhanced specific capacity, especially at high C-rates, thanks to the porous conducive carbon nanofiber matrix. Among the strategies applied to load Na₃MnZr(PO₄)₃ into the CNFs, the electrospinning (vertical setting) of the polymeric solution containing pre-synthesized Na₃MnZr(PO₄)₃ powders resulted effective in obtaining the quantitative loading of the active material and a homogeneous distribution through the sheet thickness. Notably, Na₃MnZr(PO₄)₃ aggregates connected to the CNFs, covered their surface, and were also embedded, as demonstrated by TEM and EDS. Compared to the self-standing cathodes prepared with the horizontal setting or dip–drop coating methods, the vertical binder-free electrode exhibited the highest capacity values of 78.2, 55.7, 38.8, 22.2, 16.2, 12.8, 10.3, 9.0, and 8.5 mAh/g at C-rates of 0.05C, 0.1C, 0.2C, 0.5C, 1C, 2C, 5C, 10C, and 20C, respectively, with complete capacity retention at the end of the measurements. It also exhibited a good cycling life, compared to its tape-cast counterpart: it displayed higher capacity retention at 0.2C and 1C, and, after cycling 1000 cycles at 1C, it could be further cycled at 5C, 10C, and 20C. Full article

(This article belongs to the Special Issue Modern Materials in Energy Storage and Conversion)

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26 pages, 5655 KiB

Open AccessArticle

Novel Biopolymer-Based Catalyst for the Multicomponent Synthesis of N-aryl-4-aryl-Substituted Dihydropyridines Derived from Simple and Complex Anilines

by Giovanna Bosica and Roderick Abdilla

Molecules 2024, 29(8), 1884; https://doi.org/10.3390/molecules29081884 - 20 Apr 2024

Viewed by 752

Abstract

Although Hantzsch synthesis has been an established multicomponent reaction method for more than a decade, its derivative, whereby an aniline replaces ammonium acetate as the nitrogen source, has not been explored at great length. Recent studies have shown that the products of such [...] Read more.

Although Hantzsch synthesis has been an established multicomponent reaction method for more than a decade, its derivative, whereby an aniline replaces ammonium acetate as the nitrogen source, has not been explored at great length. Recent studies have shown that the products of such a reaction, N-aryl-4-aryldihydropyridines (DHPs), have significant anticancer activity. In this study, we successfully managed to synthesize a wide range of DHPs (18 examples, 8 of which were novel) using a metal-free, mild, inexpensive, recoverable, and biopolymer-based heterogeneous catalyst, known as piperazine, which was supported in agar–agar gel. In addition, 8 further examples (3 novel) of such dihydropyridines were synthesized using isatin instead of aldehyde as a reactant, producing spiro-linked structures. Lastly, this catalyst managed to afford an unprecedented product that was derived using an innovative technique—a combination of multicomponent reactions. Essentially, the product of our previously reported aza-Friedel–Crafts multicomponent reaction could itself be used as a reactant instead of aniline in the synthesis of more complex dihydropyridines. Full article

(This article belongs to the Special Issue Multicomponent Reactions in Organic Synthesis)

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21 pages, 5431 KiB

Open AccessArticle

Increasing Analytical Quality by Designing a Thin-Layer Chromatography Scanner Method for the Determination of the Radiochemical Purity of Radiopharmaceutical Sodium Iodide ¹³¹I Oral Solution

by Miguel Vasquez-Huaman, Américo Castro-Luna, Norma Julia Ramos-Cevallos, Donald Ramos-Perfecto, Mario Alcarraz-Curi, Jacqueline Segura-Vasquez and Danny Cáceres-Antaurco

Molecules 2024, 29(8), 1883; https://doi.org/10.3390/molecules29081883 - 20 Apr 2024

Viewed by 402

Abstract

The goal of this study was to apply the principles of analytical quality by design (AQbD) to the analytical method for determining the radiochemical purity (PQR) of the radiopharmaceutical sodium iodide ¹³¹I oral solution, utilizing thin-layer chromatography (TLC) with a radio–TLC scanner, [...] Read more.

The goal of this study was to apply the principles of analytical quality by design (AQbD) to the analytical method for determining the radiochemical purity (PQR) of the radiopharmaceutical sodium iodide ¹³¹I oral solution, utilizing thin-layer chromatography (TLC) with a radio–TLC scanner, which also enables the evaluation of product quality. For AQbD, the analytical target profile (ATP), critical quality attributes (CQA), risk management, and the method operable design region (MODR) were defined through response surface methodology to optimize the method using MINITAB^® 19 software. This study encompassed the establishment of a control strategy and the validation of the method, including the assessment of selectivity, linearity, precision, robustness, detection limit, quantification limit, range, and the stability of the sample solution. Under the experimental conditions, the method parameters of the TLC scanner were experimentally demonstrated and optimized with an injection volume of 3 µL, a radioactive concentration of 10 mCi/mL, and a carrier volume of 40 µL. Statistical analysis confirmed the method’s selectivity for the ¹³¹I iodide band Rf of 0.8, a radiochemical impurity IO₃⁻ Rf of 0.6, a linearity from 6.0 to 22.0 mCi/mL, and an intermediate precision with a global relative standard deviation (RSD) of 0.624%. The method also exhibited robustness, with a global RSD of 0.101%, a detection limit of 0.09 mCi/mL, and a quantification limit of 0.53 Ci/mL, meeting the prescribed range and displaying stability over time (at 0, 2, and 20 h) with a global RSD of 0.362%, resulting in consistent outcomes. The development of a method based on AQbD facilitated the creation of a design space and an operational space, with comprehensive knowledge of the method’s characteristics and limitations. Additionally, throughout all operations, compliance with the acceptance criteria was verified. The method’s validity was confirmed under the established conditions, making it suitable for use in the manufacturing process of sodium iodide ¹³¹I and application in nuclear medicine services. Full article

(This article belongs to the Special Issue New Advances in Radiopharmaceutical Sciences)

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13 pages, 3484 KiB

Open AccessArticle

Application of Fourier-Transform Infrared Spectroscopy for the Assessment of Wine Spoilage Indicators: A Feasibility Study

by Cláudia Andreia Teixeira dos Santos, Ricardo Nuno Mendes Jorge Páscoa, Nuria Pérez-del-Notario, José Maria González-Sáiz, Consuelo Pizarro and João Almeida Lopes

Molecules 2024, 29(8), 1882; https://doi.org/10.3390/molecules29081882 - 20 Apr 2024

Viewed by 304

Abstract

Wine aroma is one of the most frequently used and explored quality indicators. Typically, its assessment involves estimating the volatile composition of wine or highly trained assessors conducting sensory analysis. However, current methodologies rely on slow, expensive and complicated analytical procedures. Additionally, sensory [...] Read more.

Wine aroma is one of the most frequently used and explored quality indicators. Typically, its assessment involves estimating the volatile composition of wine or highly trained assessors conducting sensory analysis. However, current methodologies rely on slow, expensive and complicated analytical procedures. Additionally, sensory evaluation is inherently subjective in nature. Therefore, the aim of this work is to verify the feasibility of using FTIR spectroscopy as a fast and easy methodology for the early detection of some of the most common off-odors in wines. FTIR spectroscopy was combined with partial least squares (PLS) regression for the simultaneous measurement of isoamyl alcohol, isobutanol, 1-hexanol, butyric acid, isobutyric acid, decanoic acid, ethyl acetate, furfural and acetoin. The precision and accuracy of developed calibration models (R²_P > 0.90, range error ratio > 12.1 and RPD > 3.1) proved the ability of the proposed methodology to quantify the aforementioned compounds. Full article

(This article belongs to the Special Issue The Application of Vibrational Spectroscopy Techniques Coupled with Chemometrics in Agro-Food-Pharmaceutical Products)

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14 pages, 5453 KiB

Open AccessArticle

CB1 Receptor Negative Allosteric Modulators as a Potential Tool to Reverse Cannabinoid Toxicity

by Audrey Flavin, Paniz Azizi, Natalia Murataeva, Kyle Yust, Wenwen Du, Ruth Ross, Iain Greig, Thuy Nguyen, Yanan Zhang, Ken Mackie and Alex Straiker

Molecules 2024, 29(8), 1881; https://doi.org/10.3390/molecules29081881 - 20 Apr 2024

Viewed by 443

Abstract

While the opioid crisis has justifiably occupied news headlines, emergency rooms are seeing many thousands of visits for another cause: cannabinoid toxicity. This is partly due to the spread of cheap and extremely potent synthetic cannabinoids that can cause serious neurological and cardiovascular [...] Read more.

While the opioid crisis has justifiably occupied news headlines, emergency rooms are seeing many thousands of visits for another cause: cannabinoid toxicity. This is partly due to the spread of cheap and extremely potent synthetic cannabinoids that can cause serious neurological and cardiovascular complications—and deaths—every year. While an opioid overdose can be reversed by naloxone, there is no analogous treatment for cannabis toxicity. Without an antidote, doctors rely on sedatives, with their own risks, or ‘waiting it out’ to treat these patients. We have shown that the canonical synthetic ‘designer’ cannabinoids are highly potent CB1 receptor agonists and, as a result, competitive antagonists may struggle to rapidly reverse an overdose due to synthetic cannabinoids. Negative allosteric modulators (NAMs) have the potential to attenuate the effects of synthetic cannabinoids without having to directly compete for binding. We tested a group of CB1 NAMs for their ability to reverse the effects of the canonical synthetic designer cannabinoid JWH018 in vitro in a neuronal model of endogenous cannabinoid signaling and also in vivo. We tested ABD1085, RTICBM189, and PSNCBAM1 in autaptic hippocampal neurons that endogenously express a retrograde CB1-dependent circuit that inhibits neurotransmission. We found that all of these compounds blocked/reversed JWH018, though some proved more potent than others. We then tested whether these compounds could block the effects of JWH018 in vivo, using a test of nociception in mice. We found that only two of these compounds—RTICBM189 and PSNCBAM1—blocked JWH018 when applied in advance. The in vitro potency of a compound did not predict its in vivo potency. PSNCBAM1 proved to be the more potent of the compounds and also reversed the effects of JWH018 when applied afterward, a condition that more closely mimics an overdose situation. Lastly, we found that PSNCBAM1 did not elicit withdrawal after chronic JWH018 treatment. In summary, CB1 NAMs can, in principle, reverse the effects of the canonical synthetic designer cannabinoid JWH018 both in vitro and in vivo, without inducing withdrawal. These findings suggest a novel pharmacological approach to at last provide a tool to counter cannabinoid toxicity. Full article

(This article belongs to the Section Medicinal Chemistry)

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15 pages, 2984 KiB

Open AccessArticle

Structural and Rheological Characterization of Vegetable Crispbread Enriched with Legume Purée

by Karolina Szulc and Sabina Galus

Molecules 2024, 29(8), 1880; https://doi.org/10.3390/molecules29081880 - 20 Apr 2024

Viewed by 306

Abstract

Crispbread is gaining popularity as a healthy snack or bread substitute. This is a lightweight dry type of flat food that stays fresh for a very long time due to its lack of water and usually contains different types of grain flour, including [...] Read more.

Crispbread is gaining popularity as a healthy snack or bread substitute. This is a lightweight dry type of flat food that stays fresh for a very long time due to its lack of water and usually contains different types of grain flour, including gluten-containing wheat or rye flour. The incorporation of legume purée into crispbread represents an innovative approach to enhancing the nutritional profile and taste of the product. The rheological properties of various legume purées (chickpea, white bean, black bean, and red bean) mixed with citrus pectin were examined, revealing significant differences in fluid behavior and viscosity. Crispbread formulations were analyzed for water content and activity, color, structure, FT-IR spectra, water vapor adsorption isotherms, and sensory evaluation. The results showed the possibility of obtaining crispbread based on the purée of legumes and citrus pectin. Crispbread enriched with red bean purée exhibited low water activity (0.156) and water content (3.16%), along with a continuous porous structure, and received the highest sensory evaluation score among the products. These findings can be treated as a basis for the development of other innovative recipes and combinations using legumes. Full article

(This article belongs to the Special Issue Present and Future of Food Chemistry Research: A Young Researchers’ Perspective)

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13 pages, 4788 KiB

Open AccessArticle

Chlorination of Aromatic Amino Acids: Elucidating Disinfection Byproducts, Reaction Kinetics, and Influence Factors

by Zhenyi Chen, Bangyu Chen, Hui Shen, Xunlin Li, Chen Zhou, Guangcai Ma, Xiaoxuan Wei, Xueyu Wang and Haiying Yu

Molecules 2024, 29(8), 1879; https://doi.org/10.3390/molecules29081879 - 20 Apr 2024

Viewed by 401

Abstract

In the face of ongoing water pollution challenges, the intricate interplay between dissolved organic matter and disinfectants like chlorine gives rise to potentially harmful disinfection byproducts (DBPs) during water treatment. The exploration of DBP formation originating from amino acids (AA) is a critical [...] Read more.

In the face of ongoing water pollution challenges, the intricate interplay between dissolved organic matter and disinfectants like chlorine gives rise to potentially harmful disinfection byproducts (DBPs) during water treatment. The exploration of DBP formation originating from amino acids (AA) is a critical focus of global research. Aromatic DBPs, in particular, have garnered considerable attention due to their markedly higher toxicity compared to their aliphatic counterparts. This work seeks to advance the understanding of DBP formation by investigating chlorination disinfection and kinetics using tyrosine (Tyr), phenylalanine (Phe), and tryptophan (Trp) as precursors. Via rigorous experiments, a total of 15 distinct DBPs with accurate molecular structures were successfully identified. The chlorination of all three AAs yielded highly toxic chlorophenylacetonitriles (CPANs), and the disinfectant dosage and pH value of the reaction system potentially influence chlorination kinetics. Notably, Phe exhibited the highest degradation rate compared to Tyr and Trp, at both the C_AA:C_HOCl ratio of within 1:2 and a wide pH range (6.0 to 9.0). Additionally, a neutral pH environment triggered the maximal reaction rates of the three AAs, while an acidic condition may reduce their reactivity. Overall, this study aims to augment the DBP database and foster a deeper comprehension of the DBP formation and relevant kinetics underlying the chlorination of aromatic AAs. Full article

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10 pages, 4228 KiB

Open AccessReview

Cell-Free Synthesis: Expediting Biomanufacturing of Chemical and Biological Molecules

by So-Jeong Lee and Dong-Myung Kim

Molecules 2024, 29(8), 1878; https://doi.org/10.3390/molecules29081878 - 20 Apr 2024

Viewed by 570

Abstract

The increasing demand for sustainable alternatives underscores the critical need for a shift away from traditional hydrocarbon-dependent processes. In this landscape, biomanufacturing emerges as a compelling solution, offering a pathway to produce essential chemical materials with significantly reduced environmental impacts. By utilizing engineered [...] Read more.

The increasing demand for sustainable alternatives underscores the critical need for a shift away from traditional hydrocarbon-dependent processes. In this landscape, biomanufacturing emerges as a compelling solution, offering a pathway to produce essential chemical materials with significantly reduced environmental impacts. By utilizing engineered microorganisms and biomass as raw materials, biomanufacturing seeks to achieve a carbon-neutral footprint, effectively counteracting the carbon dioxide emissions associated with fossil fuel use. The efficiency and specificity of biocatalysts further contribute to lowering energy consumption and enhancing the sustainability of the production process. Within this context, cell-free synthesis emerges as a promising approach to accelerate the shift towards biomanufacturing. Operating with cellular machinery in a controlled environment, cell-free synthesis offers multiple advantages: it enables the rapid evaluation of biosynthetic pathways and optimization of the conditions for the synthesis of specific chemicals. It also holds potential as an on-demand platform for the production of personalized and specialized products. This review explores recent progress in cell-free synthesis, highlighting its potential to expedite the transformation of chemical processes into more sustainable biomanufacturing practices. We discuss how cell-free techniques not only accelerate the development of new bioproducts but also broaden the horizons for sustainable chemical production. Additionally, we address the challenges of scaling these technologies for commercial use and ensuring their affordability, which are critical for cell-free systems to meet the future demands of industries and fully realize their potential. Full article

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23 pages, 10177 KiB

Open AccessArticle

Analysis Transcriptome and Phytohormone Changes Associated with the Allelopathic Effects of Ginseng Hairy Roots Induced by Different-Polarity Ginsenoside Components

by Tingting Zhou, Qiong Li, Xin Huang and Changbao Chen

Molecules 2024, 29(8), 1877; https://doi.org/10.3390/molecules29081877 - 19 Apr 2024

Viewed by 321

Abstract

The allelopathic autotoxicity of ginsenosides is an important cause of continuous cropping obstacles in ginseng planting. There is no report on the potential molecular mechanism of the correlation between polarity of ginsenoside components and their allelopathic autotoxicity. This study applied a combination of [...] Read more.

The allelopathic autotoxicity of ginsenosides is an important cause of continuous cropping obstacles in ginseng planting. There is no report on the potential molecular mechanism of the correlation between polarity of ginsenoside components and their allelopathic autotoxicity. This study applied a combination of metabolomics and transcriptomics analysis techniques, combined with apparent morphology, physiological indexes, and cell vitality detection of the ginseng hairy roots, through which the molecular mechanism of correlation between polarity and allelopathic autotoxicity of ginsenosides were comprehensively studied. The hairy roots of ginseng presented more severe cell apoptosis under the stress of low-polarity ginsenoside components (ZG70). ZG70 exerted allelopathic autotoxicity by regulating the key enzyme genes of cis-zeatin (cZ) synthesis pathway, indole-3-acetic acid (IAA) synthesis pathway, and jasmonates (JAs) signaling transduction pathway. The common pathway for high-polarity ginsenoside components (ZG50) and ZG70 to induce the development of allelopathic autotoxicity was through the expression of key enzymes in the gibberellin (GA) signal transduction pathway, thereby inhibiting the growth of ginseng hairy roots. cZ, indole-3-acetamid (IAM), gibberellin A1 (GA1), and jasmonoyl-L-isoleucine (JA-ILE) were the key response factors in this process. It could be concluded that the polarity of ginsenoside components were negatively correlated with their allelopathic autotoxicity. Full article

(This article belongs to the Section Natural Products Chemistry)

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16 pages, 1989 KiB

Open AccessArticle

Promising Antileishmanial Activity of Micromeria nervosa Essential Oil: In Vitro and In Silico Studies

by Rym Essid, Sarra Kefi, Bilel Damergi, Ghassen Abid, Nadia Fares, Selim Jallouli, Islem Abid, Dina Hussein, Olfa Tabbene and Ferid Limam

Molecules 2024, 29(8), 1876; https://doi.org/10.3390/molecules29081876 - 19 Apr 2024

Viewed by 303

Abstract

The present study aimed to evaluate the leishmanicidal potential of the essential oil (EO) of Micromeria (M.) nervosa and to investigate its molecular mechanism of action by qPCR. Furthermore, in silicointeraction study of the major M. nervosa EO compounds with the [...] Read more.

The present study aimed to evaluate the leishmanicidal potential of the essential oil (EO) of Micromeria (M.) nervosa and to investigate its molecular mechanism of action by qPCR. Furthermore, in silicointeraction study of the major M. nervosa EO compounds with the enzyme cytochrome P450 sterol 14α-demethylase (CYP51) was also performed. M. nervosa EO was analyzed by gas chromatography-mass spectrometry (GC-MS). Results showed that α-pinene (26.44%), t-cadinol (26.27%), caryophyllene Oxide (7.73 ± 1.04%), and α-Cadinene (3.79 ± 0.12%) are the major compounds of M. nervosa EO. However, limited antioxidant activity was observed, as this EO was ineffective in neutralizing DPPH free radicals and in inhibiting β-carotene bleaching. Interestingly, it displayed effective leishmanicidal potential against promastigote (IC₅₀ of 6.79 and 5.25 μg/mL) and amastigote (IC₅₀ of 8.04 and 7.32 μg/mL) forms of leishmania (L.) infantum and L. major, respectively. Molecular mechanism investigation showed that M. nervosa EO displayed potent inhibition on the thiol regulatory pathway. Furthermore, a docking study of the main components of the EO with cytochrome P450 sterol 14α-demethylase (CYP51) enzyme revealed that t-cadinol exhibited the best binding energy values (−7.5 kcal/mol), followed by α-cadinene (−7.3 kcal/mol) and caryophyllene oxide (−7 kcal/mol). These values were notably higher than that of the conventional drug fluconazole showing weaker binding energy (−6.9 kcal/mol). These results suggest that M. nervosa EO could serve as a potent and promising candidate for the development of alternative antileishmanial agent in the treatment of leishmaniasis. Full article

(This article belongs to the Special Issue Bioactive Compounds against Parasite, Bacteria and Related Diseases–2nd Edition)

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13 pages, 2922 KiB

Open AccessArticle

The Recognition Pathway of the SARS-CoV-2 Spike Receptor-Binding Domain to Human Angiotensin-Converting Enzyme 2

by Can Peng, Xinyue Lv, Zhiqiang Zhang, Jianping Lin and Dongmei Li

Molecules 2024, 29(8), 1875; https://doi.org/10.3390/molecules29081875 - 19 Apr 2024

Viewed by 262

Abstract

COVID-19 caused by SARS-CoV-2 has spread around the world. The receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 is a critical component that directly interacts with host ACE2. Here, we simulate the ACE2 recognition processes of RBD of the WT, Delta, and [...] Read more.

COVID-19 caused by SARS-CoV-2 has spread around the world. The receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 is a critical component that directly interacts with host ACE2. Here, we simulate the ACE2 recognition processes of RBD of the WT, Delta, and OmicronBA.2 variants using our recently developed supervised Gaussian accelerated molecular dynamics (Su-GaMD) approach. We show that RBD recognizes ACE2 through three contact regions (regions I, II, and III), which aligns well with the anchor–locker mechanism. The higher binding free energy in State d of the RBD_OmicronBA.₂-ACE2 system correlates well with the increased infectivity of OmicronBA.2 in comparison with other variants. For RBD_Delta, the T478K mutation affects the first step of recognition, while the L452R mutation, through its nearby Y449, affects the RBD_Delta-ACE2 binding in the last step of recognition. For RBD_OmicronBA.₂, the E484A mutation affects the first step of recognition, the Q493R, N501Y, and Y505H mutations affect the binding free energy in the last step of recognition, mutations in the contact regions affect the recognition directly, and other mutations indirectly affect recognition through dynamic correlations with the contact regions. These results provide theoretical insights for RBD-ACE2 recognition and may facilitate drug design against SARS-CoV-2. Full article

(This article belongs to the Special Issue Molecular Dynamics Simulations of Biomacromolecules)

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Molecules, Volume 29, Issue 8 (April-2 2024) – 219 articles

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