Molecules

28 pages, 461 KiB

Open AccessReview

Comprehensive Review on Application of FTIR Spectroscopy Coupled with Chemometrics for Authentication Analysis of Fats and Oils in the Food Products

by Abdul Rohman, Mohd Al’Ikhsan B. Ghazali, Anjar Windarsih, Irnawati, Sugeng Riyanto, Farahwahida Mohd Yusof and Shuhaimi Mustafa

Molecules 2020, 25(22), 5485; https://doi.org/10.3390/molecules25225485 - 23 Nov 2020

Cited by 46 | Viewed by 7023

Abstract

Currently, the authentication analysis of edible fats and oils is an emerging issue not only by producers but also by food industries, regulators, and consumers. The adulteration of high quality and expensive edible fats and oils as well as food products containing fats [...] Read more.

Currently, the authentication analysis of edible fats and oils is an emerging issue not only by producers but also by food industries, regulators, and consumers. The adulteration of high quality and expensive edible fats and oils as well as food products containing fats and oils with lower ones are typically motivated by economic reasons. Some analytical methods have been used for authentication analysis of food products, but some of them are complex in sampling preparation and involving sophisticated instruments. Therefore, simple and reliable methods are proposed and developed for these authentication purposes. This review highlighted the comprehensive reports on the application of infrared spectroscopy combined with chemometrics for authentication of fats and oils. New findings of this review included (1) FTIR spectroscopy combined with chemometrics, which has been used to authenticate fats and oils; (2) due to as fingerprint analytical tools, FTIR spectra have emerged as the most reported analytical techniques applied for authentication analysis of fats and oils; (3) the use of chemometrics as analytical data treatment is a must to extract the information from FTIR spectra to be understandable data. Next, the combination of FTIR spectroscopy with chemometrics must be proposed, developed, and standardized for authentication and assuring the quality of fats and oils. Full article

(This article belongs to the Special Issue Chemometrics Tools Used in Analytical Chemistry)

► Show Figures

Graphical abstract

23 pages, 3784 KiB

Open AccessArticle

Antiproliferative Homoleptic and Heteroleptic Phosphino Silver(I) Complexes: Effect of Ligand Combination on Their Biological Mechanism of Action

by Khouloud Dammak, Marina Porchia, Michele De Franco, Mirella Zancato, Houcine Naïli, Valentina Gandin and Cristina Marzano

Molecules 2020, 25(22), 5484; https://doi.org/10.3390/molecules25225484 - 23 Nov 2020

Cited by 17 | Viewed by 2626

Abstract

A series of neutral mixed-ligand [HB(pz)₃]Ag(PR₃) silver(I) complexes (PR₃ = tertiary phosphine, [HB(pz)₃]⁻ = tris(pyrazolyl)borate anion), and the corresponding homoleptic [Ag(PR₃)₄]BF₄ compounds have been synthesized and fully characterized. Silver compounds [...] Read more.

A series of neutral mixed-ligand [HB(pz)₃]Ag(PR₃) silver(I) complexes (PR₃ = tertiary phosphine, [HB(pz)₃]⁻ = tris(pyrazolyl)borate anion), and the corresponding homoleptic [Ag(PR₃)₄]BF₄ compounds have been synthesized and fully characterized. Silver compounds were screened for their antiproliferative activities against a wide panel of human cancer cells derived from solid tumors and endowed with different platinum drug sensitivity. Mixed-ligand complexes were generally more effective than the corresponding homoleptic derivatives, but the most active compounds were [HB(pz)₃]Ag(PPh₃) (5) and [Ag(PPh₃)₄]BF₄ (10), both comprising the lipophilic PPh₃ phosphine ligand. Detailed mechanistic studies revealed that both homoleptic and heteroleptic silver complexes strongly and selectively inhibit the selenoenzyme thioredoxin reductase both as isolated enzyme and in human ovarian cancer cells (half inhibition concentration values in the nanomolar range) causing the disruption of cellular thiol-redox homeostasis, and leading to apoptotic cell death. Moreover, for heteroleptic Ag(I) derivatives, an additional ability to damage nuclear DNA has been detected. These results confirm the importance of the type of silver ion coordinating ligands in affecting the biological behavior of the overall corresponding silver complexes, besides in terms of hydrophilic–lipophilic balance, also in terms of biological mechanism of action, such as interaction with DNA and/or thioredoxin reductase. Full article

(This article belongs to the Special Issue Metal-Based Drugs Ⅱ)

► Show Figures

Figure 1

14 pages, 911 KiB

Open AccessFeature PaperReview

Chagas Disease: Perspectives on the Past and Present and Challenges in Drug Discovery

by Felipe Raposo Passos Mansoldo, Fabrizio Carta, Andrea Angeli, Veronica da Silva Cardoso, Claudiu T. Supuran and Alane Beatriz Vermelho

Molecules 2020, 25(22), 5483; https://doi.org/10.3390/molecules25225483 - 23 Nov 2020

Cited by 29 | Viewed by 3158

Abstract

Chagas disease still has no effective treatment option for all of its phases despite being discovered more than 100 years ago. The development of commercial drugs has been stagnating since the 1960s, a fact that sheds light on the question of how drug [...] Read more.

Chagas disease still has no effective treatment option for all of its phases despite being discovered more than 100 years ago. The development of commercial drugs has been stagnating since the 1960s, a fact that sheds light on the question of how drug discovery research has progressed and taken advantage of technological advances. Could it be that technological advances have not yet been sufficient to resolve this issue or is there a lack of protocol, validation and standardization of the data generated by different research teams? This work presents an overview of commercial drugs and those that have been evaluated in studies and clinical trials so far. A brief review is made of recent target-based and phenotypic studies based on the search for molecules with anti-Trypanosoma cruzi action. It also discusses how proteochemometric (PCM) modeling and microcrystal electron diffraction (MicroED) can help in the case of the lack of a 3D protein structure; more specifically, Trypanosoma cruzi carbonic anhydrase. Full article

(This article belongs to the Special Issue Metalloenzyme Modulators and Enzyme Mimics: Synthesis and Applications)

► Show Figures

Figure 1

25 pages, 3373 KiB

Open AccessArticle

Chemical Characterization and Antibacterial Activity of Essential Oil of Medicinal Plants from Eastern Serbia

by Milica Aćimović, Miroslav Zorić, Valtcho D. Zheljazkov, Lato Pezo, Ivana Čabarkapa, Jovana Stanković Jeremić and Mirjana Cvetković

Molecules 2020, 25(22), 5482; https://doi.org/10.3390/molecules25225482 - 23 Nov 2020

Cited by 19 | Viewed by 3038

Abstract

The objective of this study was to evaluate wild growing Satureja kitaibelii, Thymus serpyllum, Origanum vulgare, Achillea millefolium and Achillea clypeolata with respect to their essential oil (EO) content, composition and antimicrobial activity. The five species were collected at Mt. [...] Read more.

The objective of this study was to evaluate wild growing Satureja kitaibelii, Thymus serpyllum, Origanum vulgare, Achillea millefolium and Achillea clypeolata with respect to their essential oil (EO) content, composition and antimicrobial activity. The five species were collected at Mt. Rtanj and the village of Sesalac, Eastern Serbia. The main EO constituents of Lamiaceae plants were p-cymene (24.4%), geraniol (63.4%) and germacrene D (21.5%) in Satureja kitaibelii, Thymus serpyllum and Origanum vulgare ssp. vulgare, respectively. A. millefolium EO had multiple constituents with major ones being camphor (9.8%), caryophyllene oxide (6.5%), terpinen-4-ol (6.3%) and 1,8-cineole (5.6%), while the main EO constituents of A. clypeolata were 1,8-cineole (45.1%) and camphor (18.2%). Antimicrobial testing of the EO showed that Staphylococcus aureus (Gram-positive) was more sensitive to all of the tested EOs than Escherichia coli (Gram-negative). S. kitaibelii EO showed the highest antimicrobial activity against both tested bacterial strains. This is the first study to characterize the EO composition and antimicrobial activity of these five medicinal species from Eastern Serbia in comparison with comprehensive literature data. The results can be utilized by the perfumery, cosmetics, food and pharmaceutical industries, but also for healing purposes in self-medication. Full article

► Show Figures

Figure 1

12 pages, 1455 KiB

Open AccessArticle

Src Mediates Epigallocatechin-3-O-Gallate-Elicited Acid Sphingomyelinase Activation

by Motofumi Kumazoe, Mai Kadomatsu, Jaehoon Bae, Yushi Otsuka, Yoshinori Fujimura and Hirofumi Tachibana

Molecules 2020, 25(22), 5481; https://doi.org/10.3390/molecules25225481 - 23 Nov 2020

Cited by 7 | Viewed by 2182

Abstract

Epigallocatechin-3-O-gallate (EGCG) is one of the major bioactive compounds known to be present in green tea. We previously reported that EGCG shows selective toxicity through activation of the protein kinase B (Akt)/cyclic guanosine monophosphate (cGMP)/acid sphingomyelinase (ASM) axis via targeting its [...] Read more.

Epigallocatechin-3-O-gallate (EGCG) is one of the major bioactive compounds known to be present in green tea. We previously reported that EGCG shows selective toxicity through activation of the protein kinase B (Akt)/cyclic guanosine monophosphate (cGMP)/acid sphingomyelinase (ASM) axis via targeting its receptor 67-kDa laminin receptor (67LR), which is overexpressed in cancer. However, little is known about upstream mechanisms of EGCG-elicited ASM activation. In this study we show that the proto-oncogene tyrosine-protein kinase Src, also known as c-src, plays a crucial role in the anticancer effect of EGCG. We showed that EGCG elicits phosphorylation of Src at Tyr 416, a crucial phosphorylation site for its activity, and that the pharmacological inhibition of Src impedes the upstream events in EGCG-induced cell death signaling including upregulation of Akt activity, increase in cGMP levels, and activation of ASM. Moreover, focal adhesion kinase (FAK), which is involved in the phosphorylation of Src, is colocalized with 67LR. EGCG treatment enhanced interaction of FAK and 67LR. Consistent with these findings, pharmacological inhibition of FAK significantly neutralized EGCG-induced upregulation of Akt activity and activation of ASM. Taken together, FAK/Src play crucial roles in the upstream signaling of EGCG. Full article

(This article belongs to the Special Issue Molecular Pharmacology of Green Tea)

► Show Figures

Figure 1

16 pages, 5792 KiB

Open AccessArticle

Anti-Quorum Sensing Activity of Stevia Extract, Stevioside, Rebaudioside A and Their Aglycon Steviol

by Victor Markus, Orr Share, Kerem Teralı, Nazmi Ozer, Robert S. Marks, Ariel Kushmaro and Karina Golberg

Molecules 2020, 25(22), 5480; https://doi.org/10.3390/molecules25225480 - 23 Nov 2020

Cited by 10 | Viewed by 23918

Abstract

Governments are creating regulations for consumers to reduce their sugar intake, prompting companies to increase the ratio of artificial sweeteners in their products. However, there is evidence of some deleterious effects ascribed to the aforementioned synthetic agents and therefore consumers and food manufacturers [...] Read more.

Governments are creating regulations for consumers to reduce their sugar intake, prompting companies to increase the ratio of artificial sweeteners in their products. However, there is evidence of some deleterious effects ascribed to the aforementioned synthetic agents and therefore consumers and food manufacturers have turned their attention to natural dietary sweeteners, such as stevia, to meet their sweetening needs. Stevia is generally considered safe; however, emerging scientific evidence has implicated the agent in gut microbial imbalance. In general, regulation of microbial behavior is known to depend highly on signaling molecules via quorum sensing (QS) pathways. This is also true for the gut microbial community. We, therefore, evaluated the possible role of these stevia-based natural sweeteners on this bacterial communication pathway. The use of a commercial stevia herbal supplement resulted in an inhibitory effect on bacterial communication, with no observable bactericidal effect. Purified stevia extracts, including stevioside, rebaudioside A (Reb A), and steviol revealed a molecular interaction, and possible interruption of Gram-negative bacterial communication, via either the LasR or RhlR receptor. Our in-silico analyses suggest a competitive-type inhibitory role for steviol, while Reb A and stevioside are likely to inhibit LasR-mediated QS in a non-competitive manner. These results suggest the need for further safety studies on the agents. Full article

► Show Figures

Figure 1

16 pages, 5113 KiB

Open AccessFeature PaperArticle

Water-Soluble O-, S- and Se-Functionalized Cyclic Acetyl-triaza-phosphines. Synthesis, Characterization and Application in Catalytic Azide-alkyne Cycloaddition

by Abdallah G. Mahmoud, Piotr Smoleński, M. Fátima C. Guedes da Silva and Armando J. L. Pombeiro

Molecules 2020, 25(22), 5479; https://doi.org/10.3390/molecules25225479 - 23 Nov 2020

Cited by 10 | Viewed by 2486

Abstract

The 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (DAPTA) derivatives, viz. the already reported 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane 5-oxide (DAPTA=O, 1), the novel 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane-5-sulfide (DAPTA=S, 2), and 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane-5-selenide (DAPTA=Se, 3), have been synthesized under mild conditions. They are soluble in water and most common organic solvents and have been [...] Read more.

The 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (DAPTA) derivatives, viz. the already reported 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane 5-oxide (DAPTA=O, 1), the novel 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane-5-sulfide (DAPTA=S, 2), and 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane-5-selenide (DAPTA=Se, 3), have been synthesized under mild conditions. They are soluble in water and most common organic solvents and have been characterized using ¹H and ³¹P NMR spectroscopy and, for 2 and 3, also by single crystal X-ray diffraction. The effect of O, S, or Se at the phosphorus atom on the structural features of the compounds has been investigated, also through the analyses of Hirshfeld surfaces. The presence of 1–3 enhances the activity of copper for the catalytic azide-alkyne cycloaddition reaction in an aqueous medium. The combination of cheaply available copper (II) acetate and compound 1 has been used as a catalyst for the one-pot and 1,4-regioselective procedure to obtain 1,2,3-triazoles with high yields and according to ‘click rules’. Full article

(This article belongs to the Special Issue Metal-Induced Molecule Activation and Coupling Reactions)

► Show Figures

Graphical abstract

14 pages, 4100 KiB

Open AccessArticle

Natural Approaches for Neurological Disorders—The Neuroprotective Potential of Codium tomentosum

by Joana Silva, Alice Martins, Celso Alves, Susete Pinteus, Helena Gaspar, Amparo Alfonso and Rui Pedrosa

Molecules 2020, 25(22), 5478; https://doi.org/10.3390/molecules25225478 - 23 Nov 2020

Cited by 10 | Viewed by 3090

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, and is characterized by a progressive degeneration of the dopaminergic neurons in the substantianigra. Although not completely understood, several abnormal cellular events are known to be related with PD progression, such [...] Read more.

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, and is characterized by a progressive degeneration of the dopaminergic neurons in the substantianigra. Although not completely understood, several abnormal cellular events are known to be related with PD progression, such as oxidative stress, mitochondrial dysfunction and apoptosis. Accordingly, the aim of this study was to evaluate the neuroprotective effects of Codium tomentosum enriched fractions in a neurotoxicity model mediated by 6-hydroxydopamine (6-OHDA) on SH-SY5Y human cells, and the disclosure of their mechanisms of action. Additionally, a preliminary chemical screening of the most promising bioactive fractions of C. tomentosum was carried out by GC-MS analysis. Among the tested fractions, four samples exhibited the capacity to revert the neurotoxicity induced by 6-OHDA to values higher or similar to the vitamin E (90.11 ± 3.74% of viable cells). The neuroprotective effects were mediated by the mitigation of reactive oxygen species (ROS) generation, mitochondrial dysfunctions and DNA damage, together with the reduction of Caspase-3 activity. Compounds belonging to different chemical classes, such as terpenes, alcohols, carboxylic acids, aldehydes, esters, ketones, saturated and unsaturated hydrocarbons were tentatively identified by GC-MS. The results show that C. tomentosum is a relevant source of neuroprotective agents, with particular interest for preventive therapeutics. Full article

(This article belongs to the Special Issue Advances on Natural Compounds Research: Chemistry, Biology and Biotechnology)

► Show Figures

Graphical abstract

16 pages, 1621 KiB

Open AccessCommunication

Cyst Reduction by Melatonin in a Novel Drosophila Model of Polycystic Kidney Disease

by Cassandra Millet-Boureima, Roman Rozencwaig, Felix Polyak and Chiara Gamberi

Molecules 2020, 25(22), 5477; https://doi.org/10.3390/molecules25225477 - 23 Nov 2020

Cited by 7 | Viewed by 7576

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) causes progressive cystic degeneration of the renal tubules, the nephrons, eventually severely compromising kidney function. ADPKD is incurable, with half of the patients eventually needing renal replacement. Treatments for ADPKD patients are limited and new effective therapeutics [...] Read more.

Autosomal dominant polycystic kidney disease (ADPKD) causes progressive cystic degeneration of the renal tubules, the nephrons, eventually severely compromising kidney function. ADPKD is incurable, with half of the patients eventually needing renal replacement. Treatments for ADPKD patients are limited and new effective therapeutics are needed. Melatonin, a central metabolic regulator conserved across all life kingdoms, exhibits oncostatic and oncoprotective activity and no detected toxicity. Here, we used the Bicaudal C (BicC) Drosophila model of polycystic kidney disease to test the cyst-reducing potential of melatonin. Significant cyst reduction was found in the renal (Malpighian) tubules upon melatonin administration and suggest mechanistic sophistication. Similar to vertebrate PKD, the BicC fly PKD model responds to the antiproliferative drugs rapamycin and mimics of the second mitochondria-derived activator of caspases (Smac). Melatonin appears to be a new cyst-reducing molecule with attractive properties as a potential candidate for PKD treatment. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms II)

► Show Figures

Graphical abstract

15 pages, 2828 KiB

Open AccessArticle

Cytotoxic and Antiproliferative Effects of Diarylheptanoids Isolated from Curcuma comosa Rhizomes on Leukaemic Cells

by Natsima Viriyaadhammaa, Aroonchai Saiai, Waranya Neimkhum, Wariya Nirachonkul, Wantida Chaiyana, Sawitree Chiampanichayakul, Singkome Tima, Toyonobu Usuki, Suwit Duangmano and Songyot Anuchapreeda

Molecules 2020, 25(22), 5476; https://doi.org/10.3390/molecules25225476 - 23 Nov 2020

Cited by 7 | Viewed by 2648

Abstract

Curcuma comosa belongs to the Zingiberaceae family. In this study, two natural compounds were isolated from C. comosa, and their structures were determined using nuclear magnetic resonance. The isolated compounds were identified as 7-(3,4-dihydroxyphenyl)-5-hydroxy-1-phenyl-(1E)-1-heptene (1) and trans-1,7-diphenyl-5-hydroxy-1-heptene [...] Read more.

Curcuma comosa belongs to the Zingiberaceae family. In this study, two natural compounds were isolated from C. comosa, and their structures were determined using nuclear magnetic resonance. The isolated compounds were identified as 7-(3,4-dihydroxyphenyl)-5-hydroxy-1-phenyl-(1E)-1-heptene (1) and trans-1,7-diphenyl-5-hydroxy-1-heptene (2). Compound 1 showed the strongest cytotoxicity effect against HL-60 cells, while its antioxidant and anti-inflammatory properties were stronger than those of compound 2. Compound 1 proved to be a potent antioxidant, compared to ascorbic acid. Neither compounds had any effect on red blood cell haemolysis. Furthermore, compound 1 significantly decreased Wilms’ tumour 1 protein expression and cell proliferation in KG-1a cells. Compound 1 decreased the WT1 protein levels in a time- and dose- dependent manner. Compound 1 suppressed cell cycle at the S phase. In conclusion, compound 1 has a promising chemotherapeutic potential against leukaemia. Full article

(This article belongs to the Special Issue Cytotoxic Activity of Plant Extracts)

► Show Figures

Graphical abstract

17 pages, 2799 KiB

Open AccessArticle

1,3,5-Triaryl-1,3,5-Triazinane-2,4,6-Trithiones: Synthesis, Electronic Structure and Linear Optical Properties

by Ismaël Rabouel, Nicolas Richy, Anissa Amar, Abdou Boucekkine, Thierry Roisnel, Olivier Mongin, Mark G. Humphrey and Frédéric Paul

Molecules 2020, 25(22), 5475; https://doi.org/10.3390/molecules25225475 - 23 Nov 2020

Cited by 2 | Viewed by 2389

Abstract

The synthesis of four new 1,3,5-triaryl-1,3,5-triazinane-2,4,6-trithione derivatives (thioisocyanurates) and two new partially thionated analogues from the corresponding 1,3,5-triaryl-1,3,5-triazinane-2,4,6-triones (isocyanurates) is reported, together with their spectroscopic properties. DFT calculations and comparison with the corresponding isocyanurates evidence the impact of the oxygen-for-sulfur replacement on the [...] Read more.

The synthesis of four new 1,3,5-triaryl-1,3,5-triazinane-2,4,6-trithione derivatives (thioisocyanurates) and two new partially thionated analogues from the corresponding 1,3,5-triaryl-1,3,5-triazinane-2,4,6-triones (isocyanurates) is reported, together with their spectroscopic properties. DFT calculations and comparison with the corresponding isocyanurates evidence the impact of the oxygen-for-sulfur replacement on the electronic structure and linear optical properties of these heterocycles. A bathochromic shift of the absorption bands and more efficient quenching of the fluorescence was observed. Full article

(This article belongs to the Section Photochemistry)

► Show Figures

Graphical abstract

31 pages, 1504 KiB

Open AccessReview

An Overview of Nrf2 Signaling Pathway and Its Role in Inflammation

by Sarmistha Saha, Brigitta Buttari, Emiliano Panieri, Elisabetta Profumo and Luciano Saso

Molecules 2020, 25(22), 5474; https://doi.org/10.3390/molecules25225474 - 23 Nov 2020

Cited by 564 | Viewed by 21476

Abstract

Inflammation is a key driver in many pathological conditions such as allergy, cancer, Alzheimer’s disease, and many others, and the current state of available drugs prompted researchers to explore new therapeutic targets. In this context, accumulating evidence indicates that the transcription factor Nrf2 [...] Read more.

Inflammation is a key driver in many pathological conditions such as allergy, cancer, Alzheimer’s disease, and many others, and the current state of available drugs prompted researchers to explore new therapeutic targets. In this context, accumulating evidence indicates that the transcription factor Nrf2 plays a pivotal role controlling the expression of antioxidant genes that ultimately exert anti-inflammatory functions. Nrf2 and its principal negative regulator, the E3 ligase adaptor Kelch-like ECH- associated protein 1 (Keap1), play a central role in the maintenance of intracellular redox homeostasis and regulation of inflammation. Interestingly, Nrf2 is proved to contribute to the regulation of the heme oxygenase-1 (HO-1) axis, which is a potent anti-inflammatory target. Recent studies showed a connection between the Nrf2/antioxidant response element (ARE) system and the expression of inflammatory mediators, NF-κB pathway and macrophage metabolism. This suggests a new strategy for designing chemical agents as modulators of Nrf2 dependent pathways to target the immune response. Therefore, the present review will examine the relationship between Nrf2 signaling and the inflammation as well as possible approaches for the therapeutic modulation of this pathway. Full article

(This article belongs to the Special Issue Chemistry, Biology and Pharmacology of Modulators of Oxidative Stress)

► Show Figures

Figure 1

16 pages, 1181 KiB

Open AccessReview

Exploitation of Ultrasound Technique for Enhancement of Microbial Metabolites Production

by Asma Behzadnia, Marzieh Moosavi-Nasab, Shikha Ojha and Brijesh K. Tiwari

Molecules 2020, 25(22), 5473; https://doi.org/10.3390/molecules25225473 - 23 Nov 2020

Cited by 13 | Viewed by 3746

Abstract

Microbial metabolites have significant impacts on our lives from providing valuable compounds for nutrition to agriculture and healthcare. Ever-growing demand for these natural compounds has led to the need for smart and efficient production techniques. Ultrasound is a multi-applicable technology widely exploited in [...] Read more.

Microbial metabolites have significant impacts on our lives from providing valuable compounds for nutrition to agriculture and healthcare. Ever-growing demand for these natural compounds has led to the need for smart and efficient production techniques. Ultrasound is a multi-applicable technology widely exploited in a range of industries such as chemical, medical, biotechnological, pharmaceutical, and food processes. Depending on the type of ultrasound employed, it can be used to either monitor or drive fermentation processes. Ultrasonication can improve bioproduct productivity via intensifying the performance of living organisms. Controlled ultrasonication can influence the metabolites’ biosynthesis efficiency and growth rates by improvement of cell permeability as well as mass transfer and nutrient uptake rates through cell membranes. This review contains a summarized description about suitable microbial metabolites and the applications of ultrasound technique for enhancement of the production of these metabolites as well as the associated downstream processing. Full article

(This article belongs to the Special Issue Feature Papers to Celebrate Molecules Reaches 20,000 Articles Milestone)

► Show Figures

Figure 1

17 pages, 1819 KiB

Open AccessArticle

Oleuropein Aglycone Peracetylated (3,4-DHPEA-EA(P)) Attenuates H₂O₂-Mediated Cytotoxicity in C2C12 Myocytes via Inactivation of p-JNK/p-c-Jun Signaling Pathway

by Monica Nardi, Sara Baldelli, Maria Rosa Ciriolo, Paola Costanzo, Antonio Procopio and Carmela Colica

Molecules 2020, 25(22), 5472; https://doi.org/10.3390/molecules25225472 - 23 Nov 2020

Cited by 4 | Viewed by 2148

Abstract

Oleuropein, a glycosylated secoiridoid present in olive leaves, is known to be an important antioxidant phenolic compound. We studied the antioxidant effect of low doses of oleuropein aglycone (3,4-DHPEA-EA) and oleuropein aglycone peracetylated (3,4-DHPEA-EA(P)) in murine C2C12 myocytes treated with hydrogen peroxide (H [...] Read more.

Oleuropein, a glycosylated secoiridoid present in olive leaves, is known to be an important antioxidant phenolic compound. We studied the antioxidant effect of low doses of oleuropein aglycone (3,4-DHPEA-EA) and oleuropein aglycone peracetylated (3,4-DHPEA-EA(P)) in murine C2C12 myocytes treated with hydrogen peroxide (H₂O₂). Both compounds were used at a concentration of 10 μM and were able to inhibit cell death induced by the H₂O₂ treatment, with 3,4-DHPEA-EA(P) being more. Under our experimental conditions, H₂O₂ efficiently induced the phosphorylated-active form of JNK and of its downstream target c-Jun. We demonstrated, by Western blot analysis, that 3,4-DHPEA-EA(P) was efficient in inhibiting the phospho-active form of JNK. This data suggests that the growth arrest and cell death of C2C12 proceeds via the JNK/c-Jun pathway. Moreover, we demonstrated that 3,4-DHPEA-EA(P) affects the myogenesis of C2C12 cells; because MyoD mRNA levels and the differentiation process are restored with 3,4-DHPEA-EA(P) after treatment. Overall, the results indicate that 3,4-DHPEA-EA(P) prevents ROS-mediated degenerative process by functioning as an efficient antioxidant. Full article

(This article belongs to the Special Issue Natural Organic Substances as Starting Bricks for the Semi-synthesis of New Compounds)

► Show Figures

Figure 1

10 pages, 451 KiB

Open AccessReview

Gentamicin-Coated Tibia Nail in Fractures and Nonunion to Reduce Fracture-Related Infections: A Systematic Review

by Daniele De Meo, Federico M. Cannari, Luisa Petriello, Pietro Persiani and Ciro Villani

Molecules 2020, 25(22), 5471; https://doi.org/10.3390/molecules25225471 - 23 Nov 2020

Cited by 21 | Viewed by 2526

Abstract

The incidence of a fracture-related infection (FRI) can reach 30% of open tibia fractures (OTF). The use of antibiotic-coated implants is one of the newest strategies to reduce the risk of infection in orthopedic surgery. The aim of this study was to investigate [...] Read more.

The incidence of a fracture-related infection (FRI) can reach 30% of open tibia fractures (OTF). The use of antibiotic-coated implants is one of the newest strategies to reduce the risk of infection in orthopedic surgery. The aim of this study was to investigate the efficacy and safety of a gentamicin-coated tibia nail in primary fracture fixation (FF) and revision surgery (RS) of nonunion cases in terms of FRI incidence. We conducted a systematic review according to the PRISMA checklist on Pub-Med, Cochrane, and EMBASE. Of the 32 studies, 8 were included, for a total of 203 patients treated: 114 were FF cases (63% open fractures) and 89 were RS cases, of which 43% were infected nonunion. In the FF group, four FRI were found (3.8%): three OTF (Gustilo-Anderson III) and one closed fracture; bone healing was achieved in 94% of these cases. There were four relapses of infection and one new onset in the RS group; bone healing occurred in 88% of these cases. No side effects were found. There were no significant differences in terms of FRI, nonunion, and healing between the two groups. Gentamicin-coated tibia nail is an effective therapeutic option in the prophylaxis of high-risk fracture infections and in complex nonunion cases. Full article

(This article belongs to the Special Issue Novel Biologically Active Molecules, Biomaterials and Nanoparticles for the Microbial Biofilm Control in Human Medicine)

► Show Figures

Figure 1

12 pages, 472 KiB

Open AccessArticle

Cocoa Shell as a Step Forward to Functional Chocolates—Bioactive Components in Chocolates with Different Composition

by Veronika Barišić, Milica Cvijetić Stokanović, Ivana Flanjak, Kristina Doko, Antun Jozinović, Jurislav Babić, Drago Šubarić, Borislav Miličević, Ines Cindrić and Đurđica Ačkar

Molecules 2020, 25(22), 5470; https://doi.org/10.3390/molecules25225470 - 23 Nov 2020

Cited by 13 | Viewed by 3410

Abstract

Chocolate is considered as both caloric and functional food. Its nutritional properties may be improved by addition of fiber; however, this may reduce polyphenols content. The aim of this research was to determine the influence of cocoa shell addition (as a source of [...] Read more.

Chocolate is considered as both caloric and functional food. Its nutritional properties may be improved by addition of fiber; however, this may reduce polyphenols content. The aim of this research was to determine the influence of cocoa shell addition (as a source of fiber) and its combination with different ingredients (cocoa butter equivalents (CBE), emulsifiers, dairy ingredients) on polyphenols of dark and milk chocolates. Total polyphenol (TPC) and total flavonoid (TFC) contents were determined spectrophotometrically, identification and quantification of individual compounds by high pressure liquid chromatography and antioxidant capacity by ferric reducing antioxidant power (FRAP) assay. Results showed that even though addition of cocoa shell to chocolate results in reduced contents of TPC, TFC, and individual compounds, it is not significant compared to ones reported by other authors for commercial chocolates. Other ingredients influence determined values for all investigated parameters; however, additional research is needed to reveal exact mechanisms and implications. Full article

(This article belongs to the Section Food Chemistry)

► Show Figures

Figure 1

14 pages, 712 KiB

Open AccessArticle

Anacyclus pyrethrum (L): Chemical Composition, Analgesic, Anti-Inflammatory, and Wound Healing Properties

by Fatima Zahra Jawhari, Abdelfattah El Moussaoui, Mohammed Bourhia, Hamada Imtara, Hamza Mechchate, Imane Es-Safi, Riaz Ullah, Essam Ezzeldin, Gamal A. Mostafa, Andriy Grafov, Samir Ibenmoussa, Dalila Bousta and Amina Bari

Molecules 2020, 25(22), 5469; https://doi.org/10.3390/molecules25225469 - 23 Nov 2020

Cited by 35 | Viewed by 4548

Abstract

Background: Anacyclus pyrethrum (A. pyrethrum) is a wild species belonging to the family Asteraceae, which is used in traditional medicines. Aim of the study: This work was undertaken to study the chemical composition, analgesic, anti-inflammatory, and wound healing properties of hydroalcoholic [...] Read more.

Background: Anacyclus pyrethrum (A. pyrethrum) is a wild species belonging to the family Asteraceae, which is used in traditional medicines. Aim of the study: This work was undertaken to study the chemical composition, analgesic, anti-inflammatory, and wound healing properties of hydroalcoholic extracts of different parts (roots, seeds, leaves, and capitula) of A. pyrethrum. Material and Methods: The phytochemical analysis of the studied extracts was conducted by GC-MS. The analgesic activity was evaluated in mice using acetic acid and formaldehyde methods. The anti-inflammatory activity was tested using the inhibitory method of edema induced in rats. The healing activity of the hydroethanolic extracts was explored by excision and incision wound healing models in rats. Results: The phytochemical analysis of the studied plant extracts affirmed the presence of interesting compounds, including some newly detected elements, such as sarcosine, N-(trifluoroacetyl)-butyl ester, levulinic acid, malonic acid, palmitic acid, morphinan-6-One, 4,5.alpha.-epoxy-3-hydroxy-17-methyl, 2,4-undecadiene-8,10-diyne-N-tyramide, and isovaleric acid. The extracts of different parts (roots, seeds, leaves, and capitula) exhibited promising anti-inflammatory, analgesic, and wound healing effects, with percentages of inhibition up to 98%, 94%, and 100%, respectively. Conclusion: This study might contribute towards the well-being of society as it provides evidence on the potential analgesic, anti-inflammatory, and wound healing properties of A. pyrethrum. Full article

(This article belongs to the Special Issue Plant Extracts: Biological and Pharmacological Activity—the Second Edition)

► Show Figures

Figure 1

17 pages, 2448 KiB

Open AccessArticle

Comparative Study of the Chemical Compositions and Antioxidant Activities of Fresh Juices from Romanian Cucurbitaceae Varieties

by Anna Cazanevscaia Busuioc, Andreea-Veronica Dediu Botezatu, Bianca Furdui, Costel Vinatoru, Filippo Maggi, Giovanni Caprioli and Rodica-Mihaela Dinica

Molecules 2020, 25(22), 5468; https://doi.org/10.3390/molecules25225468 - 23 Nov 2020

Cited by 32 | Viewed by 3562

Abstract

Cucurbitaceae is a family of health-promoting plants due to their compounds with beneficial effects. The aim of this study was to analyze, for the first time, the chemical composition, the antioxidant activity and the metal chelating properties of fruit juices obtained from four [...] Read more.

Cucurbitaceae is a family of health-promoting plants due to their compounds with beneficial effects. The aim of this study was to analyze, for the first time, the chemical composition, the antioxidant activity and the metal chelating properties of fruit juices obtained from four different species of the Cucurbitaceae family cultivated in Romania, namely Momordica charantia, Cucumis metuliferus, Benincasa hispida and Trichosanthes cucumerina. The samples of juice were analyzed by high-performance liquid chromatography (HPLC) and all the four species displayed high levels of the two triterpenes, oleanolic and ursolic acids, and also in phenolic compounds, including catechin, (−)-epicatechin and gallic acid. The juices demonstrated significant antioxidant activity against the free radical 2,2-diphenyl-1-picrylhydrazyl (ranging from 20 to 95%,), a good iron binding ability (ranging from 7.45 ± 0.28% to 86.95 ± 0.97%) and also promising antioxidant potential against the ABTS radical (ranging from 4.97 to 32.60 μETx/mL juice). Our findings raise interesting questions for further research on Cucurbitaceae fruit juices and, consequently, their very good antioxidant potential suggests these fruits should be further explored for their protective effect against oxidative damage. This is the first time the chemical composition and antioxidant activities of fruit juices from these four Romanian Cucurbitaceae varieties have been investigated. Full article

(This article belongs to the Special Issue Bioactive Phenolic and Polyphenolic Compounds)

► Show Figures

Graphical abstract

14 pages, 2399 KiB

Open AccessArticle

Herbal Composition LI73014F2 Alleviates Articular Cartilage Damage and Inflammatory Response in Monosodium Iodoacetate-Induced Osteoarthritis in Rats

by Hae Lim Kim, Hae Jin Lee, Dong-Ryung Lee, Bong-Keun Choi and Seung Hwan Yang

Molecules 2020, 25(22), 5467; https://doi.org/10.3390/molecules25225467 - 23 Nov 2020

Cited by 9 | Viewed by 3274

Abstract

The aim of this study was to determine the anti-osteoarthritic effects of LI73014F2, which consists of Terminalia chebula fruit, Curcuma longa rhizome, and Boswellia serrata gum resin in a 2:1:2 ratio, in the monosodium iodoacetate (MIA)-induced osteoarthritis (OA) rat model. LI73014F2 was orally [...] Read more.

The aim of this study was to determine the anti-osteoarthritic effects of LI73014F2, which consists of Terminalia chebula fruit, Curcuma longa rhizome, and Boswellia serrata gum resin in a 2:1:2 ratio, in the monosodium iodoacetate (MIA)-induced osteoarthritis (OA) rat model. LI73014F2 was orally administered once per day for three weeks. Weight-bearing distribution and arthritis index (AI) were measured once per week to confirm the OA symptoms. Synovial membrane, proteoglycan layer, and cartilage damage were investigated by histological examination, while synovial fluid interleukin-1β level was analyzed using a commercial kit. Levels of pro-inflammatory mediators/cytokines and matrix metalloproteinases (MMPs) in the cartilage tissues were investigated to confirm the anti-osteoarthritic effects of LI73014F2. LI73014F2 significantly inhibited the MIA-induced increase in OA symptoms, synovial fluid cytokine, cartilage damage, and expression levels of pro-inflammatory mediators/cytokines and MMPs in the articular cartilage. These results suggest that LI73014F2 exerts anti-osteoarthritic effects by regulating inflammatory cytokines and MMPs in MIA-induced OA rats. Full article

(This article belongs to the Special Issue New Biologically Active Substances from Plants and Animals of the Pacific Region)

► Show Figures

Figure 1

15 pages, 539 KiB

Open AccessArticle

Contents of Functionally Bioactive Peptides, Free Amino Acids, and Biogenic Amines in Dutch-Type Cheese Models Produced with Different Lactobacilli

by Monika Garbowska, Antoni Pluta and Anna Berthold-Pluta

Molecules 2020, 25(22), 5465; https://doi.org/10.3390/molecules25225465 - 22 Nov 2020

Cited by 5 | Viewed by 2129

Abstract

Cheese ripening involves a number of biochemical processes, mainly of a proteolytic nature, which are initially triggered principally by milk-coagulating enzymes and, afterward, by microorganisms or enzymes of microbial origin. The proteolytic reactions affect, primarily, the synthesis of macro- and medium-molecular peptides from [...] Read more.

Cheese ripening involves a number of biochemical processes, mainly of a proteolytic nature, which are initially triggered principally by milk-coagulating enzymes and, afterward, by microorganisms or enzymes of microbial origin. The proteolytic reactions affect, primarily, the synthesis of macro- and medium-molecular peptides from casein. In turn, the advanced proteolysis ends in the formation of short peptides and free amino acids. Further reactions may lead to the formation of nutritionally unfavorable biogenic amines. The present study aimed to determine changes in the contents of bioactive peptides (anserine and L-carnosine), free amino acids, and biogenic amines throughout the ripening of cheese models produced with the addition of Lactobacillus genus bacteria. The contents of amino acids varied considerably in the cheese models, depending on the bacterial strain added and ripening time. After five weeks of ripening, the total content of free amino acids in the cheese models ranged from 611.02 (a cheese model with Lactobacillus casei 2639) to 1596.64 mg kg⁻¹ (a cheese model with Lb. acidophilus 2499). After the same time, the contents of the total biogenic amines in the cheese models with the addition of lactobacilli were lower than in the control cheese model (except for the model with Lb. rhamnosus 489). Anserine was detected in all cheese models (79.29–119.02 mg kg⁻¹), whereas no L-carnosine was found over a five-week ripening period in the cheese models with Lb. delbrueckii 490 and Lb. casei 2639. After a five-week ripening, the highest total content of bioactive peptides was determined in the cheese models containing Lb. acidophilus 2499 (136.11 mg kg⁻¹). Full article

(This article belongs to the Special Issue Circular Economy: Agri-Food Byproducts as Source of Bioactive Compounds)

► Show Figures

Figure 1

14 pages, 879 KiB

Open AccessArticle

Steroidal Glycosides from Allium tuberosum Seeds and Their Roles in Promoting Testosterone Production of Rat Leydig Cells

by Da-Bing Zhang and Xian-Yong Wei

Molecules 2020, 25(22), 5464; https://doi.org/10.3390/molecules25225464 - 22 Nov 2020

Viewed by 1823

Abstract

A systematic phytochemical study on the components in the seeds of Allium tuberosum was performed, leading to the isolation of 27 steroidal glycosides (SGs 1–27). The structures of SGs were identified mainly by nuclear magnetic resonance and mass spectrometries as [...] Read more.

A systematic phytochemical study on the components in the seeds of Allium tuberosum was performed, leading to the isolation of 27 steroidal glycosides (SGs 1–27). The structures of SGs were identified mainly by nuclear magnetic resonance and mass spectrometries as well as the necessary chemical evidence. In the SGs, 1–10 and 22–26 are new steroidal saponin analogues. An in vitro bioassay indicates that 1, 2, 7, 8, 10, 13–15, 20, 23, and 26 display promotional roles in testosterone production of rat Leydig cells with the EC₅₀ values of 1.0 to 4.5 μM, respectively. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Graphical abstract

17 pages, 2114 KiB

Open AccessFeature PaperArticle

Synthesis, Kinetic and Conformational Studies of 2-Substituted-5-(β-d-glucopyranosyl)-pyrimidin-4-ones as Potential Inhibitors of Glycogen Phosphorylase

by Konstantinos F. Mavreas, Dionysios D. Neofytos, Evangelia D. Chrysina, Alessandro Venturini and Thanasis Gimisis

Molecules 2020, 25(22), 5463; https://doi.org/10.3390/molecules25225463 - 22 Nov 2020

Cited by 2 | Viewed by 2604

Abstract

Dysregulation of glycogen phosphorylase, an enzyme involved in glucose homeostasis, may lead to a number of pathological states such as type 2 diabetes and cancer, making it an important molecular target for the development of new forms of pharmaceutical intervention. Based on our [...] Read more.

Dysregulation of glycogen phosphorylase, an enzyme involved in glucose homeostasis, may lead to a number of pathological states such as type 2 diabetes and cancer, making it an important molecular target for the development of new forms of pharmaceutical intervention. Based on our previous work on the design and synthesis of 4-arylamino-1-(β-d-glucopyranosyl)pyrimidin-2-ones, which inhibit the activity of glycogen phosphorylase by binding at its catalytic site, we report herein a general synthesis of 2-substituted-5-(β-d-glucopyranosyl)pyrimidin-4-ones, a related class of metabolically stable, C-glucosyl-based, analogues. The synthetic development consists of a metallated heterocycle, produced from 5-bromo-2-methylthiouracil, in addition to protected d-gluconolactone, followed by organosilane reduction. The methylthio handle allowed derivatization through hydrolysis, ammonolysis and arylamine substitution, and the new compounds were found to be potent (μM) inhibitors of rabbit muscle glycogen phosphorylase. The results were interpreted with the help of density functional theory calculations and conformational analysis and were compared with previous findings. Full article

(This article belongs to the Special Issue Targeting Carbohydrate–Protein Interactions)

► Show Figures

Figure 1

14 pages, 1447 KiB

Open AccessArticle

Content of Phenolic Compounds in Meadow Vegetation and Soil Depending on the Isolation Method

by Anna Ziolkowska, Bozena Debska and Magdalena Banach-Szott

Molecules 2020, 25(22), 5462; https://doi.org/10.3390/molecules25225462 - 22 Nov 2020

Cited by 1 | Viewed by 1678

Abstract

The aim of this paper was to determine the effect of the hydrolysis method on the amounts of phenolic compounds in the plant material in soil and, as a consequence, on the parameters to determine the degree of lignins transformation in soils. The [...] Read more.

The aim of this paper was to determine the effect of the hydrolysis method on the amounts of phenolic compounds in the plant material in soil and, as a consequence, on the parameters to determine the degree of lignins transformation in soils. The study included the plant material (hay, sward, and roots) and soil—Albic Brunic Arenosol (horizon A, AE, and Bsv) samples. Phenolic compounds were isolated at two stages by applying acid hydrolysis followed by alkaline re-hydrolysis. The quantitative and qualitative analysis of phenolic compounds was performed with high-performance liquid chromatography with a DAD. The content of phenolic compounds in the extracts depended on the hydrolysis method and it was determined by the type of the research material. The amounts of phenolic compounds contained in the alkaline hydrolysates accounted for 55.7% (soil, horizon Bsv)—454% (roots) of their content in acid hydrolysates. In the extracts from acid hydrolysates, chlorogenic and p-hydroxybenzoic acids were dominant. In the alkaline extracts from the plant material, the highest content was recorded for p-coumaric and ferulic acids, and in the extracts from soil, ferulic and chlorogenic acids. A combination of acid and alkaline hydrolysis ensures the best extraction efficiency of insoluble-bound forms of polyphenols from plant and soil material. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Figure 1

20 pages, 3704 KiB

Open AccessArticle

Synthesis of Polycyclic Ether-Benzopyrans and In Vitro Inhibitory Activity against Leishmania tarentolae

by Sarita Singh, Jacob P. Grabowski, Shilpa Pohani, C. Fiore Apuzzo, David C. Platt, Marjorie A. Jones and T. Andrew Mitchell

Molecules 2020, 25(22), 5461; https://doi.org/10.3390/molecules25225461 - 21 Nov 2020

Cited by 2 | Viewed by 2053

Abstract

Construction of a focused library of polycyclic ether-benzopyrans was undertaken in order to discover new therapeutic compounds that affect Leishmania growth and infectivity. This is especially of interest since there are few drug therapies for leishmaniasis that do not have serious drawbacks such [...] Read more.

Construction of a focused library of polycyclic ether-benzopyrans was undertaken in order to discover new therapeutic compounds that affect Leishmania growth and infectivity. This is especially of interest since there are few drug therapies for leishmaniasis that do not have serious drawbacks such high cost, side effects, and emerging drug resistance. The construction of these polycyclic ether-benzopyrans utilized an acetoxypyranone-alkene [5+2] cycloaddition and the Suzuki-Miyaura cross-coupling. The multi-gram quantity of the requisite aryl bromide was obtained followed by effective Pd-catalyzed coupling with boronic acid derivatives. Compounds were tested in vitro using the parasitic protozoan, Leishmania tarentolae. Effects of concentration, time, and exposure to light were evaluated. In addition, the effects on secreted acid phosphatase activity and nitric oxide production were investigated, since both have been implicated in parasite infectivity. The data presented herein are indicative of disruption of the Leishmania tarentolae and thus provide impetus for the development and testing of a more extensive library. Full article

(This article belongs to the Special Issue Organic Synthesis in Natural Products and Bioactive Compounds)

► Show Figures

Figure 1

17 pages, 3251 KiB

Open AccessArticle

(E)-1-(Furan-2-yl)-(substituted phenyl)prop-2-en-1-one Derivatives as Tyrosinase Inhibitors and Melanogenesis Inhibition: An In Vitro and In Silico Study

by Hee Jin Jung, Sang Gyun Noh, Il Young Ryu, Chaeun Park, Ji Young Lee, Pusoon Chun, Hyung Ryong Moon and Hae Young Chung

Molecules 2020, 25(22), 5460; https://doi.org/10.3390/molecules25225460 - 21 Nov 2020

Cited by 12 | Viewed by 2479

Abstract

A series of (E)-1-(furan-2-yl)prop-2-en-1-one derivatives (compounds 1–8) were synthesized and evaluated for their mushroom tyrosinase inhibitory activity. Among these series, compound 8 (2,4-dihydroxy group bearing benzylidene) showed potent tyrosinase inhibitory activity, with respective IC₅₀ values of 0.0433 [...] Read more.

A series of (E)-1-(furan-2-yl)prop-2-en-1-one derivatives (compounds 1–8) were synthesized and evaluated for their mushroom tyrosinase inhibitory activity. Among these series, compound 8 (2,4-dihydroxy group bearing benzylidene) showed potent tyrosinase inhibitory activity, with respective IC₅₀ values of 0.0433 µM and 0.28 µM for the monophenolase and diphenolase as substrates in comparison to kojic acid as standard compound 19.97 µM and 33.47 µM. Moreover, the enzyme kinetics of compound 8 were determined to be of the mixed inhibition type and inhibition constant (K_i) values of 0.012 µM and 0.165 µM using the Lineweaver-Burk plot. Molecular docking results indicated that compound 8 can bind to the catalytic and allosteric sites 1 and 2 of tyrosinase to inhibit enzyme activity. The computational molecular dynamics analysis further revealed that compound 8 interacted with two residues in the tyrosinase active site pocket, such as ASN260 and MET280. In addition, compound 8 attenuated melanin synthesis and cellular tyrosinase activity, simulated by α-melanocyte-stimulating hormone and 1-methyl-3-isobutylxanthine. Compound 8 also decreased tyrosinase expressions in B16F10 cells. Based on in vitro and computational studies, we propose that compound 8 might be a worthy candidate for the development of an antipigmentation agent. Full article

(This article belongs to the Section Chemical Biology)

► Show Figures

Graphical abstract

19 pages, 6883 KiB

Open AccessArticle

Design, Synthesis, and Antitumor Activity of a Series of Novel 4-(Aromatic Sulfonyl)-1-oxa-4-azaspiro[4.5]deca-6,9-dien-8-ones

by Naiguo Xing, Chen Chen, Qiu Zhong, Shilong Zheng, Guangdi Wang and Ling He

Molecules 2020, 25(22), 5459; https://doi.org/10.3390/molecules25225459 - 21 Nov 2020

Cited by 2 | Viewed by 1881

Abstract

Many sulfonamides show anticancer activity. Based on benzenesulfonylazaspirodienone (HL-X9) identified in our previous work, we optimized the lead compound for better efficacy, thereby synthesizing a series of novel 4-(aromatic sulfonyl)-1-oxa-4-azaspiro[4.5]deca-6,9-dien-8-one derivatives through a key step of metal-catalyzed cascade cyclization. The preliminary antiproliferative tests [...] Read more.

Many sulfonamides show anticancer activity. Based on benzenesulfonylazaspirodienone (HL-X9) identified in our previous work, we optimized the lead compound for better efficacy, thereby synthesizing a series of novel 4-(aromatic sulfonyl)-1-oxa-4-azaspiro[4.5]deca-6,9-dien-8-one derivatives through a key step of metal-catalyzed cascade cyclization. The preliminary antiproliferative tests have shown that the anticancer activities of acetyl-protected mannose-linked sulfonylazaspirodienone derivatives (7i–7l) have been greatly improved. Among them, 7j is the most potent derivative, with IC₅₀ values of 0.17 µM, 0.05 µM, and 0.07 µM for A549, MDA-MB-231, and HeLa cell lines, respectively. Flow cytometry analysis shows that 7j arrests MDA-MB-231 cells in the G2/M phase and has a certain effect on the apoptosis of MDA-MB-231 cells. In addition, the acute toxicity of 7j was lower than that of adriamycin. Full article

(This article belongs to the Section Bioorganic Chemistry)

► Show Figures

Figure 1

18 pages, 2841 KiB

Open AccessArticle

The Potential Effects of Curcumin on Pulmonary Fibroblasts of Idiopathic Pulmonary Fibrosis (IPF)—Approaching with Next-Generation Sequencing and Bioinformatics

by Wei-An Chang, Chia-Min Chen, Chau-Chyun Sheu, Ssu-Hui Liao, Ya-Ling Hsu, Ming-Ju Tsai and Po-Lin Kuo

Molecules 2020, 25(22), 5458; https://doi.org/10.3390/molecules25225458 - 21 Nov 2020

Cited by 6 | Viewed by 3083

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease. Currently, therapeutic options are limited for this fatal disease. Curcumin, with its pleiotropic effects, has been studied for its potential therapeutic utilities in various diseases, including pulmonary fibrosis. However, the detailed [...] Read more.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease. Currently, therapeutic options are limited for this fatal disease. Curcumin, with its pleiotropic effects, has been studied for its potential therapeutic utilities in various diseases, including pulmonary fibrosis. However, the detailed mechanisms have not been studied comprehensively. We conducted a next-generation sequencing and bioinformatics study to investigate changes in the profiles of mRNA and microRNA after curcumin treatment in IPF fibroblasts. We identified 23 downregulated and 8 upregulated protein-coding genes in curcumin-treated IPF fibroblasts. Using STRING and IPA, we identified that suppression of cell cycle progression was the main cellular function associated with these differentially expressed genes. We also identified 13 downregulated and 57 upregulated microRNAs in curcumin-treated IPF fibroblasts. Further analysis identified a potential microRNA-mediated gene expression alteration in curcumin-treated IPF fibroblasts, namely, downregulated hsa-miR-6724-5p and upregulated KLF10. Therefore, curcumin might decrease the level of hsa-miR-6724-5p, leading to increased KLF10 expression, resulting in cell cycle arrest in curcumin-treated IPF fibroblasts. In conclusion, our findings might support the potential role of curcumin in the treatment of IPF, but further in-depth study is warranted to confirm our findings. Full article

► Show Figures

Graphical abstract

10 pages, 5985 KiB

Open AccessArticle

Longitudinal Bone Growth Stimulating Effect of Allium macrostemon in Adolescent Female Rats

by Hyung-Joong Kim, Sun Haeng Lee, Sung Hyun Lee, Jihong Lee, Hocheol Kim, Gyu Tae Chang and Donghun Lee

Molecules 2020, 25(22), 5449; https://doi.org/10.3390/molecules25225449 - 21 Nov 2020

Cited by 9 | Viewed by 2670

Abstract

Allium macrostemon (AM) may affect bone growth by regulating bone formation and resorption. To examine the effect of AM on bone growth, 48 rats were divided into four administration groups in which either distilled water, AM (100 and 300 mg/kg), or recombinant human [...] Read more.

Allium macrostemon (AM) may affect bone growth by regulating bone formation and resorption. To examine the effect of AM on bone growth, 48 rats were divided into four administration groups in which either distilled water, AM (100 and 300 mg/kg), or recombinant human growth hormone (rhGH; 20 μg/kg) was administered for 10 days. On day 9, all animals were intraperitoneally injected with tetracycline hydrochloride (20 mg/kg), and 48 h after the injection, the rats were sacrificed. Their tibial sections were photographed to measure bone growth. Antigen-specific immunohistochemistry was performed to detect insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2). The food intake of the AM 100 mg/kg group was higher; however, the food intake of the AM 300 mg/kg group was less than that of the control group. The rhGH and AM 100 mg/kg groups showed greater rates of bone growth (359.0 ± 23.7 and 373.1 ± 28.0 μm/day, respectively) compared with the control group. IGF-1 and BMP-2 in the AM and rhGH groups were highly expressed. Indigestion at higher doses of AM led to nonsignificant bone growth in spite of increased IGF-1 and BMP-2 expression. Therefore, a suitable amount of AM could increase bone growth. Full article

► Show Figures

Figure 1

13 pages, 296 KiB

Open AccessArticle

Anti-Microbial, Anti-Oxidant, and α-Amylase Inhibitory Activity of Traditionally-Used Medicinal Herbs: A Comparative Analyses of Pharmacology, and Phytoconstituents of Regional Halophytic Plants’ Diaspora

by Mohsen S. Al-Omar, Hamdoon A. Mohammed, Salman A. A. Mohammed, Essam Abd-Elmoniem, Yasser I. Kandil, Hussein M. Eldeeb, Sridevi Chigurupati, Ghassan M. Sulaiman, Hadeel K. Al-Khurayyif, Basma S. Almansour, Prarthana M. Suryavamshi and Riaz A. Khan

Molecules 2020, 25(22), 5457; https://doi.org/10.3390/molecules25225457 - 20 Nov 2020

Cited by 23 | Viewed by 3528

Abstract

Halophytes are the category of plants growing under harsh conditions of super-salinity, and are wide-spread in the coastal Mediterranean climatic conditions and desert oasis. They are adept at surviving through maintaining excessive production of enzymatic, and non-enzymatic secondary metabolites, especially phenolics and flavonoids [...] Read more.

Halophytes are the category of plants growing under harsh conditions of super-salinity, and are wide-spread in the coastal Mediterranean climatic conditions and desert oasis. They are adept at surviving through maintaining excessive production of enzymatic, and non-enzymatic secondary metabolites, especially phenolics and flavonoids that primarily work as anti-oxidants and phytoalexins. Five major halophyte species growing in the kingdom’s Qassim’s high-salted desert regions were investigated for confirming their traditionally used biological activity of sugar-control and anti-infectious properties. In this context, the comparative presence of phenolics, and flavonoids together with anti-microbial, anti-oxidants, and the anti-diabetic potentials of the plants’ extracts were investigated through the α-amylase inhibition method. The highest concentrations of phenolics and flavonoids were detected in Salsola imbricata (360 mg/g of the extract as Gallic-Acid-Equivalents/GAE, and 70.5 mg/g of the extract as Rutin-Equivalents/RE). In contrast, the lowest concentrations of phenolics and flavonoids were detected in Salsola cyclophylla (126.6 mg/g GAE, and 20.5 mg/g RE). The halophytes were found rich in trace elements, a factor for water-retention in high-salinity plants, wherein iron and zinc elements were found comparatively in higher concentrations in Aeluropus lagopoides (4113 µg/kg, and 40.1 µg/kg, respectively), while the copper was detected in higher concentration (11.1 µg/kg) in S. imbricata, analyzed through Inductively Coupled Plasma Optical Emission Spectrometric (ICP-OES) analysis. The anti-oxidant potentials and α-amylase enzyme inhibition-based anti-diabetic activity of S. imbricata was significantly higher than the other halophytes under study, wherein S. cyclophylla exhibited the lowest level of α-amylase inhibition. The maximum DPPH radicals’ (52.47 mg/mL), and α-amylase inhibitions (IC₅₀ 22.98 µg/mL) were detected in A.lagopoides. The anti-microbial activity against the Methicillin-Resistant Staphylococcus aureus was strongly exhibited by Zygophyllum simplex (33 mm Inhibition Zone-Diameter, 50 µg/mL Minimum-Inhibitory-Concentration), while Escherichia coli, Enterococcus faecalis, and Candida albicans growths were moderately inhibited by Tamarix aphylla. The current findings exhibited significant differences among the locally distributed halophytic plants species with regards to their bioactivity levels, anti-oxidant potentials, and the presence of trace elements. The ongoing data corroborated the plants’ traditional uses in infections and diabetic conditions. The enhanced local distribution of the plants’ diaspora and higher density of occurrence of these plants species in this region, in comparison to their normal climatic condition’s counterparts, seemed to be affected by humans’ use of the species as part of the traditional and alternative medicine over a period of long time. Full article

(This article belongs to the Special Issue Plant Extracts: Biological and Pharmacological Activity—the Second Edition)

20 pages, 3980 KiB

Open AccessArticle

Ultrasound-Assisted Deep Eutectic Solvent Extraction of Anthocyanins from Blueberry Wine Residues: Optimization, Identification, and HepG2 Antitumor Activity

by Hongkun Xue, Jiaqi Tan, Qian Li, Jintian Tang and Xu Cai

Molecules 2020, 25(22), 5456; https://doi.org/10.3390/molecules25225456 - 20 Nov 2020

Cited by 19 | Viewed by 2743

Abstract

Blueberry wine residues produced during the wine-brewing process contain abundant anthocyanins and other bioactive compounds. To extract anthocyanins from blueberry wine residues more efficiently, a novel procedure of ultrasound-assisted deep eutectic solvent extraction (UADESE) was proposed in this work. The extraction process was [...] Read more.

Blueberry wine residues produced during the wine-brewing process contain abundant anthocyanins and other bioactive compounds. To extract anthocyanins from blueberry wine residues more efficiently, a novel procedure of ultrasound-assisted deep eutectic solvent extraction (UADESE) was proposed in this work. The extraction process was optimized by response surface methodology coupled with genetic algorithm. The optimum extraction parameters to achieve the highest yield of anthocyanins (9.32 ± 0.08 mg/g) from blueberry wine residues by UADESE were obtained at water content of 29%, ultrasonic power of 380 W, extraction temperature of 55 °C, and extraction time of 40 min. The AB-8 macroporous resin combined with Sephadex LH-20 techniques was used to purify the crude extract (CE) obtained under optimum extraction conditions and analyze the anthocyanins composition by HPLC-ESI-MS/MS. The cyanidin-3-rutinoside with purity of 92.81% was obtained. The HepG2 antitumor activity of CE was better than that of the purified anthocyanins component. Moreover, CE could increase the intracellular reactive oxygen species levels and the apoptosis, and arrest HepG2 cells in the S phases. These findings provided an effective and feasible method for anthocyanins extraction, and reduced the environmental burden of this waste. Full article

(This article belongs to the Special Issue Anthocyanins: Extraction, Purification and Applications)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Molecules, Volume 25, Issue 22 (November-2 2020) – 265 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI