Molecules

11 pages, 2661 KiB

Open AccessArticle

Benefits of the Hydrophobic Surface for CH₃NH₃PbI₃ Crystalline Growth towards Highly Efficient Inverted Perovskite Solar Cells

by Yang Li, Zheng Xu, Suling Zhao, Dandan Song, Bo Qiao, Youqin Zhu and Juan Meng

Molecules 2019, 24(10), 2027; https://doi.org/10.3390/molecules24102027 - 27 May 2019

Cited by 18 | Viewed by 4367

Abstract

In inverted perovskite solar cells (PSCs), high-quality perovskite film grown on hole-transporting material (HTM) with pinhole-free coverage and a large grain size is crucial for high efficiency. Here, we report on the growth of pinhole-free and large grain CH₃NH₃PbI [...] Read more.

In inverted perovskite solar cells (PSCs), high-quality perovskite film grown on hole-transporting material (HTM) with pinhole-free coverage and a large grain size is crucial for high efficiency. Here, we report on the growth of pinhole-free and large grain CH₃NH₃PbI₃ crystals favored by a hydrophobic small molecular HTM, namely, 4,4′-Bis(4-(di-p-toyl)aminostyryl)biphenyl (TPASBP). The hydrophobic surface induced by TPASBP suppressed the density of the perovskite nuclei and heterogeneous nucleation, thus promoting the perovskite to grow into a dense and homogeneous film with a large grain size. The CH₃NH₃PbI₃ deposited on the TPASBP exhibited better crystallization and a lower trap density than that on the hydrophilic surface of indium tin oxide (ITO), resulting in a significant reduction in carrier recombination. Combined with the efficient hole extraction ability of TPASBP, a high efficiency of 18.72% in the inverted PSCs fabricated on TPASBP was achieved. Full article

(This article belongs to the Special Issue Advanced Materials for Solar Energy)

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14 pages, 2335 KiB

Open AccessArticle

Novel Nucleic Acid Binding Small Molecules Discovered Using DNA-Encoded Chemistry

by Alexander Litovchick, Xia Tian, Michael I. Monteiro, Kaitlyn M. Kennedy, Marie-Aude Guié, Paolo Centrella, Ying Zhang, Matthew A. Clark and Anthony D. Keefe

Molecules 2019, 24(10), 2026; https://doi.org/10.3390/molecules24102026 - 27 May 2019

Cited by 25 | Viewed by 6056

Abstract

Inspired by the many reported successful applications of DNA-encoded chemical libraries in drug discovery projects with protein targets, we decided to apply this platform to nucleic acid targets. We used a 120-billion-compound set of 33 distinct DNA-encoded chemical libraries and affinity-mediated selection to [...] Read more.

Inspired by the many reported successful applications of DNA-encoded chemical libraries in drug discovery projects with protein targets, we decided to apply this platform to nucleic acid targets. We used a 120-billion-compound set of 33 distinct DNA-encoded chemical libraries and affinity-mediated selection to discover binders to a panel of DNA targets. Here, we report the successful discovery of small molecules that specifically interacted with DNA G-quartets, which are stable structural motifs found in G-rich regions of genomic DNA, including in the promoter regions of oncogenes. For this study, we chose the G-quartet sequence found in the c-myc promoter as a primary target. Compounds enriched using affinity-mediated selection against this target demonstrated high-affinity binding and high specificity over DNA sequences not containing G-quartet motifs. These compounds demonstrated a moderate ability to discriminate between different G-quartet motifs and also demonstrated activity in a cell-based assay, suggesting direct target engagement in the cell. DNA-encoded chemical libraries and affinity-mediated selection are uniquely suited to discover binders to targets that have no inherent activity outside of a cellular context, and they may also be of utility in other nucleic acid structural motifs. Full article

(This article belongs to the Special Issue DNA-Encoded Chemical Libraries)

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38 pages, 2219 KiB

Open AccessReview

Applications of Photonics in Agriculture Sector: A Review

by Jin Yeong Tan, Pin Jern Ker, K. Y. Lau, M. A. Hannan and Shirley Gee Hoon Tang

Molecules 2019, 24(10), 2025; https://doi.org/10.3390/molecules24102025 - 27 May 2019

Cited by 33 | Viewed by 6152

Abstract

The agricultural industry has made a tremendous contribution to the foundations of civilization. Basic essentials such as food, beverages, clothes and domestic materials are enriched by the agricultural industry. However, the traditional method in agriculture cultivation is labor-intensive and inadequate to meet the [...] Read more.

The agricultural industry has made a tremendous contribution to the foundations of civilization. Basic essentials such as food, beverages, clothes and domestic materials are enriched by the agricultural industry. However, the traditional method in agriculture cultivation is labor-intensive and inadequate to meet the accelerating nature of human demands. This scenario raises the need to explore state-of-the-art crop cultivation and harvesting technologies. In this regard, optics and photonics technologies have proven to be effective solutions. This paper aims to present a comprehensive review of three photonic techniques, namely imaging, spectroscopy and spectral imaging, in a comparative manner for agriculture applications. Essentially, the spectral imaging technique is a robust solution which combines the benefits of both imaging and spectroscopy but faces the risk of underutilization. This review also comprehends the practicality of all three techniques by presenting existing examples in agricultural applications. Furthermore, the potential of these techniques is reviewed and critiqued by looking into agricultural activities involving palm oil, rubber, and agro-food crops. All the possible issues and challenges in implementing the photonic techniques in agriculture are given prominence with a few selective recommendations. The highlighted insights in this review will hopefully lead to an increased effort in the development of photonics applications for the future agricultural industry. Full article

(This article belongs to the Special Issue Advances in Near Infrared Spectroscopy and Related Computational Methods)

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16 pages, 4158 KiB

Open AccessArticle

Preparation, In Vivo and In Vitro Release of Polyethylene Glycol Monomethyl Ether-Polymandelic Acid Microspheres Loaded Panax Notoginseng Saponins

by Yi He, Hongli Li, Xiangyu Zheng, Mingwei Yuan, Renyu Yang, Minglong Yuan and Cui Yang

Molecules 2019, 24(10), 2024; https://doi.org/10.3390/molecules24102024 - 27 May 2019

Cited by 8 | Viewed by 3167

Abstract

In order to enrich the types of Panax notoginseng saponins (PNS) sustained-release preparations and provide a new research idea for the research and development of traditional Chinese medicine sustained-release formulations, a series of Panax notoginseng saponins microspheres was prepared by a double emulsion [...] Read more.

In order to enrich the types of Panax notoginseng saponins (PNS) sustained-release preparations and provide a new research idea for the research and development of traditional Chinese medicine sustained-release formulations, a series of Panax notoginseng saponins microspheres was prepared by a double emulsion method using a series of degradable amphiphilic macromolecule materials polyethylene glycol monomethyl ether-polymandelic acid (mPEG-PMA) as carrier. The structure and molecular weight of the series of mPEG-PMA were determined by nuclear magnetic resonance spectroscopy (¹ HNMR) and gel chromatography (GPC). The results of the appearance, particle size, drug loading and encapsulation efficiency of the drug-loaded microspheres show that the mPEG10000-PMA (1:9) material is more suitable as a carrier for loading the total saponins of Panax notoginseng. The particle size was 2.51 ± 0.21 μm, the drug loading and encapsulation efficiency were 8.54 ± 0.16% and 47.25 ± 1.64%, respectively. The drug-loaded microspheres were used for in vitro release and degradation experiments to investigate the degradation and sustained release behaviour of the drug-loaded microspheres. The biocompatibility of the microspheres was studied by haemolytic, anticoagulant and cytotoxicity experiments. The pharmacological activity of the microspheres was studied by anti-inflammatory and anti-tumour experiments. The results showed that the drug-loaded microspheres could be released stably for about 12 days and degraded within 60 days. At the same time, the microspheres had good biocompatibility, anti-inflammatory and anti-tumour activities. Full article

(This article belongs to the Special Issue Smart Polymers for Delivery of Bioactive Molecules)

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14 pages, 2336 KiB

Open AccessArticle

Preparation, Characterization, and Release Kinetics of Chitosan-Coated Nanoliposomes Encapsulating Curcumin in Simulated Environments

by Mahmoud Hasan, Kamil Elkhoury, Cyril J. F. Kahn, Elmira Arab-Tehrany and Michel Linder

Molecules 2019, 24(10), 2023; https://doi.org/10.3390/molecules24102023 - 27 May 2019

Cited by 87 | Viewed by 6254

Abstract

Curcumin, a natural polyphenol, has many biological properties, such as anti-inflammatory, antioxidant, and anti-carcinogenic properties, yet, its sensitivity to light, oxygen, and heat, and its low solubility in water renders its preservation and bioavailability challenging. To increase its bioaccessibility, we fabricated nanoliposomes and [...] Read more.

Curcumin, a natural polyphenol, has many biological properties, such as anti-inflammatory, antioxidant, and anti-carcinogenic properties, yet, its sensitivity to light, oxygen, and heat, and its low solubility in water renders its preservation and bioavailability challenging. To increase its bioaccessibility, we fabricated nanoliposomes and chitosan-coated nanoliposomes encapsulating curcumin, and we evaluated the systems in terms of their physicochemical characteristics and release profiles in simulated gastrointestinal mediums. Chitosan-coating enhanced the stability of nanoliposomes and slowed the release of curcumin in the simulated gastrointestinal (GI) environment. This study demonstrates that nanoliposomes and chitosan-coated nanoliposomes are promising carriers for poorly soluble lipophilic compounds with low oral bioavailability, such as curcumin. Full article

(This article belongs to the Special Issue Chitosan-Based Nanomaterials for Biomedical Applications)

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14 pages, 2967 KiB

Open AccessArticle

Hypermongone C Accelerates Wound Healing through the Modulation of Inflammatory Factors and Promotion of Fibroblast Migration

by Sara E. Moghadam, Mahdi Moridi Farimani, Sara Soroury, Samad N. Ebrahimi and Ehsan Jabbarzadeh

Molecules 2019, 24(10), 2022; https://doi.org/10.3390/molecules24102022 - 27 May 2019

Cited by 13 | Viewed by 3203

Abstract

The physiology of wound healing is dependent on the crosstalk between inflammatory mediators and cellular components of skin regeneration including fibroblasts and endothelial cells. Therefore, strategies to promote healing must regulate this crosstalk to achieve maximum efficacy. In light of the remarkable potential [...] Read more.

The physiology of wound healing is dependent on the crosstalk between inflammatory mediators and cellular components of skin regeneration including fibroblasts and endothelial cells. Therefore, strategies to promote healing must regulate this crosstalk to achieve maximum efficacy. In light of the remarkable potential of natural compounds to target multiple signaling mechanisms, this study aims to demonstrate the potential of hypermongone C, a polycyclic polyprenylated acylphloroglucinol (PPAP), to accelerate wound closure by concurrently enhancing fibroblast proliferation and migration, promoting angiogenesis, and suppressing pro-inflammatory cytokines. This compound belongs to a family of plants (Hypericum) that traditionally have been used to treat injuries. Nevertheless, the exact biological evidence to support the claims is still missing. The results were obtained using a traditional model of cell scratch assay and endothelial cell tube formation, combined with the analysis of protein and gene expression by macrophages. In summary, the data suggest that hypermongone C is a multi-targeting therapeutic natural compound for the promotion of tissue repair and the regulation of inflammation. Full article

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14 pages, 8559 KiB

Open AccessArticle

Discovery of (3-Benzyl-5-hydroxyphenyl)carbamates as New Antitubercular Agents with Potent In Vitro and In Vivo Efficacy

by Ya-Juan Cheng, Zhi-Yong Liu, Hua-Ju Liang, Cui-Ting Fang, Niu-Niu Zhang, Tian-Yu Zhang and Ming Yan

Molecules 2019, 24(10), 2021; https://doi.org/10.3390/molecules24102021 - 27 May 2019

Cited by 5 | Viewed by 3387

Abstract

A series of 3-amino-5-benzylphenol derivatives were designed and synthesized. Among them, (3-benzyl-5-hydroxyphenyl)carbamates were found to exert good inhibitory activity against M. tuberculosis H37Ra, H37Rv and clinically isolated multidrug-resistant M. tuberculosis strains (MIC = 0.625–6.25 μg/mL). The privileged compounds 3i and 3l showed moderate [...] Read more.

A series of 3-amino-5-benzylphenol derivatives were designed and synthesized. Among them, (3-benzyl-5-hydroxyphenyl)carbamates were found to exert good inhibitory activity against M. tuberculosis H37Ra, H37Rv and clinically isolated multidrug-resistant M. tuberculosis strains (MIC = 0.625–6.25 μg/mL). The privileged compounds 3i and 3l showed moderate cytotoxicity against cell line A549. Compound 3l also exhibited potent in vivo inhibitory activity on a mouse infection model via the oral administration. The results demonstrated 3-hydroxyphenylcarbamates as a class of new antitubercular agents with good potential. Full article

(This article belongs to the Special Issue Tuberculosis Drug Discovery and Development)

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12 pages, 1774 KiB

Open AccessArticle

Picroside II Isolated from Pseudolysimachion rotundum var. subintegrum Inhibits Glucocorticoid Refractory Serum Amyloid A (SAA) Expression and SAA-induced IL-33 Secretion

by Kiram Lee, Jin Choi, Bo Kyong Choi, Young-Mi Gu, Hyung Won Ryu, Sei-Ryang Oh and Hyun-Jun Lee

Molecules 2019, 24(10), 2020; https://doi.org/10.3390/molecules24102020 - 27 May 2019

Cited by 6 | Viewed by 3028

Abstract

Chronic obstructive pulmonary disease (COPD) is a major inflammatory lung disease characterized by irreversible and progressive airflow obstruction. Although corticosteroids are often used to reduce inflammation, steroid therapies are insufficient in patients with refractory COPD. Both serum amyloid A (SAA) and IL-33 have [...] Read more.

Chronic obstructive pulmonary disease (COPD) is a major inflammatory lung disease characterized by irreversible and progressive airflow obstruction. Although corticosteroids are often used to reduce inflammation, steroid therapies are insufficient in patients with refractory COPD. Both serum amyloid A (SAA) and IL-33 have been implicated in the pathology of steroid-resistant lung inflammation. Picroside II isolated from Pseudolysimachion rotundum var. subintegrum (Plantaginaceae) is a major bioactive component of YPL-001, which has completed phase-2a clinical trials in chronic obstructive pulmonary disease patients. In this study, we investigated whether picroside II is effective in treating steroid refractory lung inflammation via the inhibition of the SAA-IL-33 axis. Picroside II inhibited LPS-induced SAA1 expression in human monocytes, which are resistant to steroids. SAA induced the secretion of IL-33 without involving cell necrosis. Picroside II, but not dexamethasone effectively inhibited SAA-induced IL-33 expression and secretion. The inhibitory effect by picroside II was mediated by suppressing the mitogen-activated protein kinase (MAPK) p38, ERK1/2, and nuclear factor-κB pathways. Our results suggest that picroside II negatively modulates the SAA-IL-33 axis that has been implicated in steroid-resistant lung inflammation. These findings provide valuable information for the development of picroside II as an alternative therapeutic agent against steroid refractory lung inflammation in COPD. Full article

(This article belongs to the Special Issue Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry-II)

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19 pages, 2299 KiB

Open AccessArticle

Importance of the Proximity and Orientation of Ligand-Linkage to the Design of Cinnamate-GW9662 Hybrid Compounds as Covalent PPARγ Agonists

by Yuki Utsugi, Hirona Kobuchi, Yukio Kawamura, Ahmed Salahelden Aboelhamd Atito, Masaya Nagao, Hiroko Isoda and Yusaku Miyamae

Molecules 2019, 24(10), 2019; https://doi.org/10.3390/molecules24102019 - 27 May 2019

Cited by 4 | Viewed by 4709

Abstract

Covalent agonists of PPARγ cause unique receptor conformational changes and behave as selective PPARγ modulators, whereas there are few covalent agonists other than endogenous unsaturated fatty acids metabolites. Previously, we established a cell-based strategy to identify new PPARγ ligands and synthesized a new-type [...] Read more.

Covalent agonists of PPARγ cause unique receptor conformational changes and behave as selective PPARγ modulators, whereas there are few covalent agonists other than endogenous unsaturated fatty acids metabolites. Previously, we established a cell-based strategy to identify new PPARγ ligands and synthesized a new-type of covalent agonist that possesses the hybrid structure of a plant-derived cinnamic acid derivative and GW9662, a covalent antagonist. Herein, we report six analogues that differ in how the two fragments are linked together. Compounds with a simplified linker showed potent agonistic activity with improved EC₅₀ values (less than 5 nM), indicating that close proximity between the two fragments improves binding affinity. When the position of cinnamic acid moiety was placed at 4′ carbon of aniline ring, PPARγ agonist activity was completely abolished. Docking studies suggested that the activation profile likely depends on interaction with the cavity around helix 3, β-sheet, and Ω-loop region in the ligand-binding domain. Furthermore, a cell-based assay revealed that agonist-type compounds activate PPARγ transcription in a manner dependent on covalent linkage with the Cys285 residue leading to prolonged transactivation. This activation feature reflects pharmacological benefits of covalent drugs, suggesting that these hybrid compounds may serve as potential leads for a new-class of covalent PPARγ ligands. Full article

(This article belongs to the Section Medicinal Chemistry)

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23 pages, 6474 KiB

Open AccessArticle

The Effect of Pressure on Halogen Bonding in 4-Iodobenzonitrile

by Nico Giordano, Sergejs Afanasjevs, Christine M. Beavers, Claire L. Hobday, Konstantin V. Kamenev, Earl F. O’Bannon, Javier Ruiz-Fuertes, Simon J. Teat, Rafael Valiente and Simon Parsons

Molecules 2019, 24(10), 2018; https://doi.org/10.3390/molecules24102018 - 27 May 2019

Cited by 11 | Viewed by 4087

Abstract

The crystal structure of 4-iodobenzonitrile, which is monoclinic (space group I2/a) under ambient conditions, contains chains of molecules linked through C≡N···I halogen-bonds. The chains interact through CH···I, CH···N and π-stacking contacts. The crystal structure remains in the same phase up [...] Read more.

The crystal structure of 4-iodobenzonitrile, which is monoclinic (space group I2/a) under ambient conditions, contains chains of molecules linked through C≡N···I halogen-bonds. The chains interact through CH···I, CH···N and π-stacking contacts. The crystal structure remains in the same phase up to 5.0 GPa, the b axis compressing by 3.3%, and the a and c axes by 12.3 and 10.9 %. Since the chains are exactly aligned with the crystallographic b axis these data characterise the compressibility of the I···N interaction relative to the inter-chain interactions, and indicate that the halogen bond is the most robust intermolecular interaction in the structure, shortening from 3.168(4) at ambient pressure to 2.840(1) Å at 5.0 GPa. The π∙∙∙π contacts are most sensitive to pressure, and in one case the perpendicular stacking distance shortens from 3.6420(8) to 3.139(4) Å. Packing energy calculations (PIXEL) indicate that the π∙∙∙π interactions have been distorted into a destabilising region of their potentials at 5.0 GPa. The structure undergoes a transition to a triclinic (

P \bar{1}

) phase at 5.5 GPa. Over the course of the transition, the initially colourless and transparent crystal darkens on account of formation of microscopic cracks. The resistance drops by 10% and the optical transmittance drops by almost two orders of magnitude. The I···N bond increases in length to 2.928(10) Å and become less linear [<C−I∙∙∙N = 166.2(5)°]; the energy stabilises by 2.5 kJ mol⁻¹ and the mixed C-I/I..N stretching frequency observed by Raman spectroscopy increases from 249 to 252 cm⁻¹. The driving force of the transition is shown to be relief of strain built-up in the π∙∙∙π interactions rather than minimisation of the molar volume. The triclinic phase persists up to 8.1 GPa. Full article

(This article belongs to the Special Issue High–Pressure Behaviour of Solids: From Molecular Species to 3D-Framework Materials)

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11 pages, 1408 KiB

Open AccessReview

Nanotechnology Approaches in Tackling Cardiovascular Diseases

by Ray Putra Prajnamitra, Hung-Chih Chen, Chen-Ju Lin, Li-Lun Chen and Patrick Ching-Ho Hsieh

Molecules 2019, 24(10), 2017; https://doi.org/10.3390/molecules24102017 - 27 May 2019

Cited by 32 | Viewed by 5244

Abstract

Cardiovascular diseases have continued to remain a leading cause of mortality and morbidity worldwide. Poor proliferation capability of adult cardiomyocytes disables the heart from regenerating new myocardium after a myocardial ischaemia event and therefore weakens the heart in the long term, which may [...] Read more.

Cardiovascular diseases have continued to remain a leading cause of mortality and morbidity worldwide. Poor proliferation capability of adult cardiomyocytes disables the heart from regenerating new myocardium after a myocardial ischaemia event and therefore weakens the heart in the long term, which may result in heart failure and death. Delivery of cardioprotective therapeutics soon after the event can help to protect the heart from further cell death and improve cardiac function, but delivery methods and potential side effects of these therapeutics may be an issue. Advances in nanotechnology, particularly nanoparticles for drug delivery, have enabled researchers to obtain better drug targeting capability, thus increasing the therapeutic outcome. Detailed study of nanoparticles in vivo is useful as it can provide insight for future treatments. Nanogel can help to create a more favourable environment, not only for a sustained delivery of therapeutics, but also for a better navigation of the therapeutics to the targeted sites. Finally, if the damage to the myocardium is too severe for drug treatment, nanopatch can help to improve cardiac function and healing by becoming a platform for pluripotent stem cell-derived cardiomyocytes to grow for the purpose of cell-based regenerative therapy. Full article

(This article belongs to the Special Issue Cardiovascular Nanomedicines and Nanomaterials )

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13 pages, 3621 KiB

Open AccessArticle

Astragalus Polysaccharide RAP Induces Macrophage Phenotype Polarization to M1 via the Notch Signaling Pathway

by Wei Wei, Zhi-Peng Li, Zhao-Xiang Bian and Quan-Bin Han

Molecules 2019, 24(10), 2016; https://doi.org/10.3390/molecules24102016 - 27 May 2019

Cited by 57 | Viewed by 4684

Abstract

Macrophages occur in polarized phenotypes, whose characteristics determine the role they play in tumor growth. The M1 phenotype macrophages promote tumoricidal responses and suppress tumor growth. Our previous study showed that a polysaccharide isolated from Radix Astragali, named RAP, was itself non-cytotoxic but [...] Read more.

Macrophages occur in polarized phenotypes, whose characteristics determine the role they play in tumor growth. The M1 phenotype macrophages promote tumoricidal responses and suppress tumor growth. Our previous study showed that a polysaccharide isolated from Radix Astragali, named RAP, was itself non-cytotoxic but induced RAW264.7 cells’ cytotoxicity against cancer cells. The current study was undertaken to determine its mechanism. Series studies was conducted to show that RAP is able to induce much higher gene expression of M1 markers, including iNOS, IL-6, TNF-a, and CXCL10, compared with the control group. When RAP-induced BMDMs were transplanted together with 4T1 tumor cells in BALB/c mice, both tumor volume and tumor weight decreased. Further studies indicated that RAP induces the Notch signaling pathway in RAW264.7 cells. The function of Notch signaling in macrophage polarization was confirmed by using γ-secretase inhibitor. These results suggested that Astragalus polysaccharide RAP induces macrophage’s polarization to M1 phenotype via the Notch signaling pathway. Full article

(This article belongs to the Special Issue Bioactive Molecules and Their Mechanisms of Action)

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8 pages, 2096 KiB

Open AccessArticle

Disassembly of Dimeric Cyanine Dye Supramolecular Assembly by Tetramolecular G-quadruplex Dependence on Linker Length and Layers of G-quartet

by Lijia Yu, Yansong Zhang, Chunguang Ding and Xiaodong Shi

Molecules 2019, 24(10), 2015; https://doi.org/10.3390/molecules24102015 - 27 May 2019

Cited by 3 | Viewed by 2976

Abstract

Cyanine dyes have been widely applied in various biological systems owing to their specific photochemical properties. Assembly and disassembly process of cyanine dyes were constructed and regulated by special biomolecules. In this paper, dimeric cyanine dyes with different repeat units (oligo-oxyethylene) in linker [...] Read more.

Cyanine dyes have been widely applied in various biological systems owing to their specific photochemical properties. Assembly and disassembly process of cyanine dyes were constructed and regulated by special biomolecules. In this paper, dimeric cyanine dyes with different repeat units (oligo-oxyethylene) in linker (TC-Pn) (n = 3–6) were found to form H-aggregates or mixture aggregates in PBS. These aggregates could be disassembled into dimer and/or monomer by (TGnT) tetramolecular G-quadruplexes (n = 3–6, 8), which were affected by the linker length of dimeric cyanine dyes and layers of G-quartets. The ¹H-NMR titration results suggest that the binding mode of dimeric cyanine dye with TGnT might be on both ends—stacking like a clip. This binding mode could clearly explain that matching structures between dimeric cyanine dyes and TGnT quadruplexes could regulate the disassembly properties of aggregates. These results could provide clues for the development of highly specific G-quadruplex probes. Full article

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9 pages, 1194 KiB

Open AccessArticle

Permeabilities of CO₂, H₂S and CH₄ through Choline-Based Ionic Liquids: Atomistic-Scale Simulations

by Abdukarem Amhamed, Mert Atilhan and Golibjon Berdiyorov

Molecules 2019, 24(10), 2014; https://doi.org/10.3390/molecules24102014 - 27 May 2019

Cited by 17 | Viewed by 3254

Abstract

Molecular dynamics simulations are used to study the transport of CO

_{2}

, H

_{2}

S and CH

_{4}

molecules across environmentally friendly choline-benzoate and choline-lactate ionic liquids (ILs). The permeability coefficients of the considered molecules are calculated using the free energy and [...] Read more.

Molecular dynamics simulations are used to study the transport of CO

_{2}

, H

_{2}

S and CH

_{4}

molecules across environmentally friendly choline-benzoate and choline-lactate ionic liquids (ILs). The permeability coefficients of the considered molecules are calculated using the free energy and diffusion rate profiles. Both systems show the largest resistance to CH

_{4}

, whereas more than 5 orders of magnitude larger permeability coefficients are obtained for the other two gas molecules. The CO

_{2}

/CH

_{4}

and H

_{2}

S/CH

_{4}

selectivity was estimated to be more than 10

^{4}

and 10

^{5}

, respectively. These results indicate the great potential of the considered ILs for greenhouse gas control. Full article

(This article belongs to the Special Issue Deep Eutectic Solvents)

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18 pages, 4635 KiB

Open AccessArticle

Optimization of Ultrasonic-Assisted Extraction and Purification of Rhein from Cassia fistula Pod Pulp

by Bancha Yingngam, Haiyu Zhao, Bian Baolin, Nipawan Pongprom and Adelheid Brantner

Molecules 2019, 24(10), 2013; https://doi.org/10.3390/molecules24102013 - 26 May 2019

Cited by 9 | Viewed by 3476

Abstract

Rhein is used as an active ingredient in laxatives in medicinal herbal products and is a chemical marker for quality control purposes. Thus, a simple and effective method for the optimized extraction of a high amount of rhein from the fruit pulp of [...] Read more.

Rhein is used as an active ingredient in laxatives in medicinal herbal products and is a chemical marker for quality control purposes. Thus, a simple and effective method for the optimized extraction of a high amount of rhein from the fruit pulp of Cassia fistula was investigated using ultrasonic-assisted extraction (UAE). The response surface methodology was applied to find the most suitable parameters for optimizing the extraction process and to study the factors’ relationships with each other. The best conditions for ultrasonic extraction were the application of 1:40 g/mL solid-to-liquid ratio and 10% EtOH–H₂O as a solvent at 75 °C for 40 min. This method was compared to a conventional decoction in two variations. In these experiments, it was confirmed that the UAE was more favorable than the decoction methods. The resulting crude extract was further purified by liquid–liquid extraction with a basic pH adjustment, followed by recrystallization. High-purity rhein was obtained by using chromatographic techniques and nuclear magnetic resonance spectroscopy. Therefore, this study suggests that UAE is an efficient alternative method for the extraction of rhein from C. fistula pod pulp. The resulting optimized conditions can be applied as a useful tool for the large-scale industrial production of a rhein-rich plant extract. Full article

(This article belongs to the Section Natural Products Chemistry)

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15 pages, 3768 KiB

Open AccessArticle

Cytostatic and Cytotoxic Natural Products against Cancer Cell Models

by Taotao Ling, Walter H. Lang, Julie Maier, Marizza Quintana Centurion and Fatima Rivas

Molecules 2019, 24(10), 2012; https://doi.org/10.3390/molecules24102012 - 26 May 2019

Cited by 20 | Viewed by 6012

Abstract

The increasing prevalence of drug resistant and/or high-risk cancers indicate further drug discovery research is required to improve patient outcome. This study outlines a simplified approach to identify lead compounds from natural products against several cancer cell lines, and provides the basis to [...] Read more.

The increasing prevalence of drug resistant and/or high-risk cancers indicate further drug discovery research is required to improve patient outcome. This study outlines a simplified approach to identify lead compounds from natural products against several cancer cell lines, and provides the basis to better understand structure activity relationship of the natural product cephalotaxine. Using high-throughput screening, a natural product library containing fractions and pure compounds was interrogated for proliferation inhibition in acute lymphoblastic leukemia cellular models (SUP-B15 and KOPN-8). Initial hits were verified in control and counter screens, and those with EC₅₀ values ranging from nanomolar to low micromolar were further characterized via mass spectrometry, NMR, and cytotoxicity measurements. Most of the active compounds were alkaloid natural products including cephalotaxine and homoharringtonine, which were validated as protein synthesis inhibitors with significant potency against several cancer cell lines. A generated BODIPY-cephalotaxine probe provides insight into the mode of action of cephalotaxine and further rationale for its weaker potency when compared to homoharringtonine. The steroidal natural products (ecdysone and muristerone A) also showed modest biological activity and protein synthesis inhibition. Altogether, these findings demonstrate that natural products continue to provide insight into structure and function of molecules with therapeutic potential against drug resistant cancer cell models. Full article

(This article belongs to the Special Issue Antitumoral Properties of Natural Products)

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14 pages, 2177 KiB

Open AccessArticle

Danggui Buxue Decoction Sensitizes the Response of Non-Small-Cell Lung Cancer to Gemcitabine via Regulating Deoxycytidine Kinase and P-glycoprotein

by Xiyang Sun, Xin Xu, Yanfei Chen, Rong Guan, Tingting Cheng, Ye Wang, Rui Jin, Min Song and Taijun Hang

Molecules 2019, 24(10), 2011; https://doi.org/10.3390/molecules24102011 - 25 May 2019

Cited by 26 | Viewed by 3688

Abstract

This study aimed to investigate whether the anti-tumor effect of gemcitabine (GEM) in non-small-cell lung cancer (NSCLC) treatment was affected by Danggui Buxue decoction (DBD), and explore the potential mechanisms. The combined use of GEM and DBD showed an enhanced tumor growth inhibition [...] Read more.

This study aimed to investigate whether the anti-tumor effect of gemcitabine (GEM) in non-small-cell lung cancer (NSCLC) treatment was affected by Danggui Buxue decoction (DBD), and explore the potential mechanisms. The combined use of GEM and DBD showed an enhanced tumor growth inhibition effect in a murine Lewis lung carcinoma (LLC) model. LC-MS/MS results showed that the pharmacokinetic behaviors of a GEM active metabolite, gemcitabine triphosphate (dFdCTP), were found to be altered remarkably in the peripheral blood mononuclear cells (PBMC) of DBD co-administration rats. In addition, after co-administration of DBD with GEM, Western Blot and qPCR results confirmed that the expression of deoxycytidine kinase (dCK) in tumor tissues of LLC-bearing mice were markedly increased. DBD co-administration also reversed the upregulation of P-glycoprotein (P-gp) in tumor tissues induced by GEM. Moreover, DBD could notably up-regulate the IL-12p70 and GM-CSF expression in mice serum, suggesting potential immunomodulatory activities in tumor-bearing mice. Meanwhile, DBD inhibited the P-gp efflux activity in A549 cells. Therefore, the regulation of dCK and P-gp played important roles in the alternation of GEM pharmacokinetics and the enhancement of the anti-tumor effect of GEM. DBD being a potential dCK promoter could work as an adjuvant agent to boost the anticancer effect of GEM. Full article

(This article belongs to the Special Issue Herb–Drug Interactions: Current Progress and Future Trends)

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16 pages, 2032 KiB

Open AccessArticle

Aldose Reductase, Protein Glycation Inhibitory and Antioxidant of Peruvian Medicinal Plants: The Case of Tanacetum parthenium L. and Its Constituents

by Seung Hwan Hwang, Hyun-Yong Kim, Yanymee N. Guillen Quispe, Zhiqiang Wang, Guanglei Zuo and Soon Sung Lim

Molecules 2019, 24(10), 2010; https://doi.org/10.3390/molecules24102010 - 25 May 2019

Cited by 15 | Viewed by 3716

Abstract

Diabetes complications, including peripheral neuropathy, cataracts, impaired wound healing, vascular damage, arterial wall stiffening and retinopathy diseases, are among the most predominant health problems facing the world’s population today. The 22 Peruvian plant extracts were screened for their potential inhibitory activity against rat [...] Read more.

Diabetes complications, including peripheral neuropathy, cataracts, impaired wound healing, vascular damage, arterial wall stiffening and retinopathy diseases, are among the most predominant health problems facing the world’s population today. The 22 Peruvian plant extracts were screened for their potential inhibitory activity against rat lens aldose reductase (RLAR) and DPPH radical scavenging. Among them, we have found that Tanacetum parthenium L. (TP) has the RLAR, AGEs and DPPH radical scavenging activities. We used for screening of active components in TP against RLAR and DPPH for the first time by ultrafiltration (UF) and DPPH. Compounds in TP were isolated by Sephadex column chromatography and their structures were established by MS and NMR spectroscopic analyses. Among the isolated compounds, ferulic acid, apigenin, luteolin-7-O-glucoside, luteolin, chrysosplenol, and kaempferol showed potent inhibition with IC₅₀ values of 1.11–3.20 and 6.44–16.23 μM for RLAR and DPPH radical scavenging. Furthermore, these compounds suppressed sorbitol accumulation in rat lenses and ferulic acid, luteolin-7-O-glucoside, and luteolin have AGEs inhibitory activities with IC₅₀ values of 3.43–6.73 μM. In summary, our study provides interesting plants for further study with respect to the treatment and prevention of diabetic complication of Peruvian plant and can provide the scientific base of the traditional uses. Full article

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16 pages, 3312 KiB

Open AccessArticle

Effects of β-glucosidase and α-rhamnosidase on the Contents of Flavonoids, Ginkgolides, and Aroma Components in Ginkgo Tea Drink

by Xianying Fang, Yurong Dong, Yingying Xie, Lei Wang, Jingqiu Wang, Yuechen Liu, Linguo Zhao and Fuliang Cao

Molecules 2019, 24(10), 2009; https://doi.org/10.3390/molecules24102009 - 25 May 2019

Cited by 23 | Viewed by 3230

Abstract

Ginkgo tea is a kind of health food produced from Ginkgo biloba leaves. The market of Ginkgo tea encountered many difficulties because of its bad palatability and vague function statement. In this study, two kinds of glycosidase were used to improve the flavor [...] Read more.

Ginkgo tea is a kind of health food produced from Ginkgo biloba leaves. The market of Ginkgo tea encountered many difficulties because of its bad palatability and vague function statement. In this study, two kinds of glycosidase were used to improve the flavor of Ginkgo tea, and three kinds of bioactivities were selected to investigate the health care function of the tea infusion. The aroma components extracted by headspace absorb (HSA) method during the making of Ginkgo tea were analyzed by GC-MS. The flavonoids and ginkgolides released into the tea infusion were studied by HPLC. A combination of β-glucosidase (β-G) and α-rhamnosidase (α-R) was applied during the making of the tea. The contents of characteristic aroma components and the release of total flavonoids and ginkgolides were increased significantly by adding β-G and α-R. The composition of flavone glycosides was changed greatly. The free radical scavenging, inhibition of inflammatory cell activation, and tumor cytotoxicity activities of the tea were demonstrably improved. According to the release of active components, Ginkgo tea can be brewed repeatedly for at least three times. The enzymes used here show potential application prospects in the making of Ginkgo tea or tea drink to get higher contents of flavonoids, ginkgolides, and aroma components. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 1161 KiB

Open AccessArticle

Effect of Chitosan and Fish Gelatin Coatings on Preventing the Deterioration and Preserving the Quality of Fresh-Cut Apples

by Yung-Shin Shyu, Guan-Wen Chen, Shao-Ching Chiang and Wen-Chieh Sung

Molecules 2019, 24(10), 2008; https://doi.org/10.3390/molecules24102008 - 25 May 2019

Cited by 12 | Viewed by 3384

Abstract

The effect of fish gelatin and chitosan coatings on the physicochemical characteristics of fresh-cut apples (Malus pumila Mill.), stored at 5 °C and 22 °C, was investigated. Chitosan provided an effective control for microbial growth, maintained firmness during 4 days of storage [...] Read more.

The effect of fish gelatin and chitosan coatings on the physicochemical characteristics of fresh-cut apples (Malus pumila Mill.), stored at 5 °C and 22 °C, was investigated. Chitosan provided an effective control for microbial growth, maintained firmness during 4 days of storage at room temperature (22 °C), and 12 days at refrigerator (5 °C). The results indicated that chitosan coating caused a significant decrease (p < 0.05) in the L* value of cube color of cut apples. Fish gelatin–chitosan coatings mitigated the L* value and decrease in hue angle of the cut apple samples, at cold storage. Experimental results showed that fish gelatin–chitosan and chitosan coatings, can be used to mitigate the formation of vitamin C, due to respiration, microbial growth, and weight loss at cold storage. Fish gelatin–chitosan coating might be a better combination for maintaining appearance and extending shelf-life of cut apples, compared to only chitosan coatings. Full article

(This article belongs to the Special Issue Gelatin: Chemistry, Characterization, Application)

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22 pages, 2984 KiB

Open AccessArticle

Activity and Thermal Stability of Cobalt(II)-Based Olefin Polymerization Catalysts Adorned with Sterically Hindered Dibenzocycloheptyl Groups

by Muhammad Zada, Liwei Guo, Yanping Ma, Wenjuan Zhang, Zygmunt Flisak, Yang Sun and Wen-Hua Sun

Molecules 2019, 24(10), 2007; https://doi.org/10.3390/molecules24102007 - 25 May 2019

Cited by 24 | Viewed by 2720

Abstract

Five examples of unsymmetrical 2-(2,4-bis(dibenzocycloheptyl)-6-methylphenyl- imino)ethyl)-6-(1-(arylyimino)ethyl)pyridine derivatives (aryl = 2,6-Me₂C₆H₃ in L1; 2,6-Et₂C₆H₃ in L2; 2,6-i-Pr₂C₆H₃ in L3; 2,4,6-Me₃C₆H₂ in [...] Read more.

Five examples of unsymmetrical 2-(2,4-bis(dibenzocycloheptyl)-6-methylphenyl- imino)ethyl)-6-(1-(arylyimino)ethyl)pyridine derivatives (aryl = 2,6-Me₂C₆H₃ in L1; 2,6-Et₂C₆H₃ in L2; 2,6-i-Pr₂C₆H₃ in L3; 2,4,6-Me₃C₆H₂ in L4 and 2,6-Et₂-4-MeC₆H₂ in L5) were prepared and characterized. Treatment with CoCl₂ offered the corresponding cobalt precatalysts Co1–Co5, which were characterized by FT-IR and NMR spectroscopy as well as elemental analysis. The molecular structures of Co3 and Co4 determined by single crystal X-ray diffraction revealed distorted square pyramidal geometries with τ₅ values of 0.052–0.215. Activated with either MAO or MMAO, the precatalysts displayed high activities in ethylene polymerization, where Co1 with the least bulky substituents exhibited a peak activity of 1.00 × 10⁷ g PE mol⁻¹ (Co) h⁻¹ at 60 °C. With MAO as a cocatalyst, the activity was reduced only by one order of magnitude at 90 °C, which implies thermally stable active sites. The polymerization product was highly linear polyethylene with vinyl end groups. Co3 with the most sterically hindered active sites was capable of generating polyethylene of high molecular weight, reaching 6.46 × 10⁵ g mol⁻¹. Furthermore, high melting point and unimodal molecular weight distribution were observed in the resulting polyethylene. It must be stressed that the thermal stability of the catalyst and the molecular weight of the obtained polyethylene attain the highest values reported for the unsymmetrical 2,6-bis(imino)pyridylcobalt (II) chloride precatalysts. Full article

(This article belongs to the Special Issue Well-Defined Metal Complex Catalysts for Olefin Polymerization)

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22 pages, 4854 KiB

Open AccessArticle

Multiclass Classifier for P-Glycoprotein Substrates, Inhibitors, and Non-Active Compounds

by Liadys Mora Lagares, Nikola Minovski and Marjana Novič

Molecules 2019, 24(10), 2006; https://doi.org/10.3390/molecules24102006 - 25 May 2019

Cited by 19 | Viewed by 4833

Abstract

P-glycoprotein (P-gp) is a transmembrane protein that actively transports a wide variety of chemically diverse compounds out of the cell. It is highly associated with the ADMET (absorption, distribution, metabolism, excretion and toxicity) properties of drugs/drug candidates and contributes to decreasing toxicity by [...] Read more.

P-glycoprotein (P-gp) is a transmembrane protein that actively transports a wide variety of chemically diverse compounds out of the cell. It is highly associated with the ADMET (absorption, distribution, metabolism, excretion and toxicity) properties of drugs/drug candidates and contributes to decreasing toxicity by eliminating compounds from cells, thereby preventing intracellular accumulation. Therefore, in the drug discovery and toxicological assessment process it is advisable to pay attention to whether a compound under development could be transported by P-gp or not. In this study, an in silico multiclass classification model capable of predicting the probability of a compound to interact with P-gp was developed using a counter-propagation artificial neural network (CP ANN) based on a set of 2D molecular descriptors, as well as an extensive dataset of 2512 compounds (1178 P-gp inhibitors, 477 P-gp substrates and 857 P-gp non-active compounds). The model provided a good classification performance, producing non error rate (NER) values of 0.93 for the training set and 0.85 for the test set, while the average precision (AvPr) was 0.93 for the training set and 0.87 for the test set. An external validation set of 385 compounds was used to challenge the model’s performance. On the external validation set the NER and AvPr values were 0.70 for both indices. We believe that this in silico classifier could be effectively used as a reliable virtual screening tool for identifying potential P-gp ligands. Full article

(This article belongs to the Special Issue Receptor-Dependent QSAR Methods)

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16 pages, 2855 KiB

Open AccessArticle

The Up-Regulation of Oxidative Stress as a Potential Mechanism of Novel MAO-B Inhibitors for Glioblastoma Treatment

by Guya Diletta Marconi, Marialucia Gallorini, Simone Carradori, Paolo Guglielmi, Amelia Cataldi and Susi Zara

Molecules 2019, 24(10), 2005; https://doi.org/10.3390/molecules24102005 - 25 May 2019

Cited by 20 | Viewed by 3655

Abstract

Gliomas are malignant brain tumors characterized by rapid spread and growth into neighboring tissues and graded I–IV by the World Health Organization. Glioblastoma is the fastest growing and most devastating IV glioma. The aim of this paper is to evaluate the biological effects [...] Read more.

Gliomas are malignant brain tumors characterized by rapid spread and growth into neighboring tissues and graded I–IV by the World Health Organization. Glioblastoma is the fastest growing and most devastating IV glioma. The aim of this paper is to evaluate the biological effects of two potent and selective Monoamine Oxidase B (MAO-B) inhibitors, Cmp3 and Cmp5, in C6 glioma cells and in CTX/TNA2 astrocytes in terms of cell proliferation, apoptosis occurrence, inflammatory events and cell migration. These compounds decrease C6 glioma cells viability sparing normal astrocytes. Cell cycle analysis, the Mitochondrial Membrane Potential (MMP) and Reactive Oxygen Species (ROS) production were detected, revealing that Cmp3 and Cmp5 induce a G1 or G2/M cell cycle arrest, as well as a MMP depolarization and an overproduction of ROS; moreover, they inhibit the expression level of inducible nitric oxide synthase 2, thus contributing to fatal drug-induced oxidative stress. Cmp5 notably reduces glioma cell migration via down-regulating Matrix Metalloproteinases 2 and 9. This study demonstrated that our novel MAO-B inhibitors increase the oxidative stress level resulting in a cell cycle arrest and markedly reduces glioma cells migration thus reinforcing the hypothesis of a critical role-played by MAO-B in mediating oncogenesis in high-grade gliomas. Full article

(This article belongs to the Special Issue Recent Advances in Anticancer Drugs)

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6 pages, 678 KiB

Open AccessCommunication

The Difference in Cytotoxic Activity between Two Optical Isomers of Gelsemine from Gelsemium elegans Benth. on PC12 Cells

by Li Lin, Yan-Chun Liu and Zhao-Ying Liu

Molecules 2019, 24(10), 2004; https://doi.org/10.3390/molecules24102004 - 25 May 2019

Cited by 3 | Viewed by 2614

Abstract

Two optical isomers, +/− gelsemine (1, 2), together with one known compound were isolated from the whole plant of G. elegans. The structures of the separated constituents were elucidated on 1D and 2D (¹H-¹H COSY, HMBC, HSQC) NMR [...] Read more.

Two optical isomers, +/− gelsemine (1, 2), together with one known compound were isolated from the whole plant of G. elegans. The structures of the separated constituents were elucidated on 1D and 2D (¹H-¹H COSY, HMBC, HSQC) NMR spectroscopy and high-resolution mass spectrometry (HRMS). The isolated alkaloids were tested in vitro for cytotoxic potential against PC12 cells by the MTT assay. As a result, (+) gelsemine (compound 1) exhibited cytotoxic activity against PC12 cells with an IC₅₀ value of 31.59 μM, while (−) gelsemine (compound 2) was not cytotoxic. Full article

(This article belongs to the Special Issue Natural Products as Tools in Drug Discovery and Development)

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12 pages, 1978 KiB

Open AccessArticle

Effects of Diethyl Phosphate, a Non-Specific Metabolite of Organophosphorus Pesticides, on Serum Lipid, Hormones, Inflammation, and Gut Microbiota

by Fangwei Yang, Jinwang Li, Guofang Pang, Fazheng Ren and Bing Fang

Molecules 2019, 24(10), 2003; https://doi.org/10.3390/molecules24102003 - 24 May 2019

Cited by 39 | Viewed by 4372

Abstract

Organophosphorus pesticides (OPs) can be metabolized to diethyl phosphate (DEP) in the gut environment, which may affect the immune and endocrine systems and the microbiota. Correlations between OPs and diseases have been established by epidemiological studies, mainly based on the contents of their [...] Read more.

Organophosphorus pesticides (OPs) can be metabolized to diethyl phosphate (DEP) in the gut environment, which may affect the immune and endocrine systems and the microbiota. Correlations between OPs and diseases have been established by epidemiological studies, mainly based on the contents of their metabolites, including DEP, in the serum or urine. However, the effects of DEP require further study. Therefore, in this study, adult male rats were exposed to 0.08 or 0.13 mg/kg DEP for 20 weeks. Serum levels of hormones, lipids, and inflammatory cytokines as well as gut microbiota were measured. DEP significantly enriched opportunistic pathogens, including Paraprevotella, Parabacteroides, Alloprevotella, and Helicobacter, leading to a decrease in interleukin-6 (IL-6). Exposure to the high dose of DEP enriched the butyrate-producing genera, Alloprevotella and Intestinimonas, leading to an increase in estradiol and a resulting decrease in total triglycerides (TGs) and low-density lipoprotein cholesterol (LDL-C); meanwhile, DEP-induced increases in peptide tyrosine‒tyrosine (PYY) and ghrelin were attributed to the enrichment of short-chain fatty acid-producing Clostridium sensu stricto 1 and Lactobacillus. These findings indicate that measuring the effects of DEP is not a proxy for measuring the effects of its parent compounds. Full article

(This article belongs to the Section Chemical Biology)

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30 pages, 12620 KiB

Open AccessArticle

Exploring African Medicinal Plants for Potential Anti-Diabetic Compounds with the DIA-DB Inverse Virtual Screening Web Server

by Andreia S.P. Pereira, Helena den Haan, Jorge Peña-García, Marién M. Moreno, Horacio Pérez-Sánchez and Zeno Apostolides

Molecules 2019, 24(10), 2002; https://doi.org/10.3390/molecules24102002 - 24 May 2019

Cited by 29 | Viewed by 6038

Abstract

Medicinal plants containing complex mixtures of several compounds with various potential beneficial biological effects are attractive treatment interventions for a complex multi-faceted disease like diabetes. In this study, compounds identified from African medicinal plants were evaluated for their potential anti-diabetic activity. A total [...] Read more.

Medicinal plants containing complex mixtures of several compounds with various potential beneficial biological effects are attractive treatment interventions for a complex multi-faceted disease like diabetes. In this study, compounds identified from African medicinal plants were evaluated for their potential anti-diabetic activity. A total of 867 compounds identified from over 300 medicinal plants were screened in silico with the DIA-DB web server (http://bio-hpc.eu/software/dia-db/) against 17 known anti-diabetic drug targets. Four hundred and thirty compounds were identified as potential inhibitors, with 184 plants being identified as the sources of these compounds. The plants Argemone ochroleuca, Clivia miniata, Crinum bulbispermum, Danais fragans, Dioscorea dregeana, Dodonaea angustifolia, Eucomis autumnalis, Gnidia kraussiana, Melianthus comosus, Mondia whitei, Pelargonium sidoides, Typha capensis, Vinca minor, Voacanga africana, and Xysmalobium undulatum were identified as new sources rich in compounds with a potential anti-diabetic activity. The major targets identified for the natural compounds were aldose reductase, hydroxysteroid 11-beta dehydrogenase 1, dipeptidyl peptidase 4, and peroxisome proliferator-activated receptor delta. More than 30% of the compounds had five or more potential targets. A hierarchical clustering analysis coupled with a maximum common substructure analysis revealed the importance of the flavonoid backbone for predicting potential activity against aldose reductase and hydroxysteroid 11-beta dehydrogenase 1. Filtering with physiochemical and the absorption, distribution, metabolism, excretion and toxicity (ADMET) descriptors identified 28 compounds with favorable ADMET properties. The six compounds—crotofoline A, erythraline, henningsiine, nauclefidine, vinburnine, and voaphylline—were identified as novel potential multi-targeted anti-diabetic compounds, with favorable ADMET properties for further drug development. Full article

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39 pages, 2117 KiB

Open AccessReview

Hydroxytyrosol, Tyrosol and Derivatives and Their Potential Effects on Human Health

by Ana Karković Marković, Jelena Torić, Monika Barbarić and Cvijeta Jakobušić Brala

Molecules 2019, 24(10), 2001; https://doi.org/10.3390/molecules24102001 - 24 May 2019

Cited by 311 | Viewed by 16197

Abstract

The Mediterranean diet and olive oil as its quintessential part are almost synonymous with a healthy way of eating and living nowadays. This kind of diet has been highly appreciated and is widely recognized for being associated with many favorable effects, such as [...] Read more.

The Mediterranean diet and olive oil as its quintessential part are almost synonymous with a healthy way of eating and living nowadays. This kind of diet has been highly appreciated and is widely recognized for being associated with many favorable effects, such as reduced incidence of different chronic diseases and prolonged longevity. Although olive oil polyphenols present a minor fraction in the composition of olive oil, they seem to be of great importance when it comes to the health benefits, and interest in their biological and potential therapeutic effects is huge. There is a growing body of in vitro and in vivo studies, as well as intervention-based clinical trials, revealing new aspects of already known and many new, previously unknown activities and health effects of these compounds. This review summarizes recent findings regarding biological activities, metabolism and bioavailability of the major olive oil phenolic compounds—hydroxytyrosol, tyrosol, oleuropein, oleocanthal and oleacein—the most important being their antiatherogenic, cardioprotective, anticancer, neuroprotective and endocrine effects. The evidence presented in the review concludes that these phenolic compounds have great pharmacological potential, however, further studies are still required. Full article

(This article belongs to the Special Issue Olive Bioactives: From Molecules to Human Health)

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1 pages, 490 KiB

Open AccessCorrection

Correction: Mishra, S.K. and Suryaprakash, N. Intramolecular Hydrogen Bonding Involving Organic Fluorine: NMR Investigations Corroborated by DFT-Based Theoretical Calculations: Molecules 2017, 22, 423

by Sandeep Kumar Mishra and N. Suryaprakash

Molecules 2019, 24(10), 2000; https://doi.org/10.3390/molecules24102000 - 24 May 2019

Cited by 1 | Viewed by 2177

Abstract

The authors wish to make the following corrections to their paper [...] Full article

(This article belongs to the Special Issue Intramolecular Hydrogen Bonding 2017)

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19 pages, 4046 KiB

Open AccessArticle

Phenolic Compounds from Populus alba L. and Salix subserrata Willd. (Salicaceae) Counteract Oxidative Stress in Caenorhabditis elegans

by Nora Tawfeek, Mansour Sobeh, Dalia I. Hamdan, Nawaal Farrag, Mariana Roxo, Assem M. El-Shazly and Michael Wink

Molecules 2019, 24(10), 1999; https://doi.org/10.3390/molecules24101999 - 24 May 2019

Cited by 28 | Viewed by 4460

Abstract

Utilizing bioassay- and TLC-guided column chromatography, fifteen secondary metabolites from Populus alba and eight compounds from Salix subserrata were isolated, including a novel plant metabolite salicyl ether and characterized using ultralviolet light (UV) absorbance, mass spectrometry (MS), ¹H-, ¹³C-NMR (nuclear magnetic [...] Read more.

Utilizing bioassay- and TLC-guided column chromatography, fifteen secondary metabolites from Populus alba and eight compounds from Salix subserrata were isolated, including a novel plant metabolite salicyl ether and characterized using ultralviolet light (UV) absorbance, mass spectrometry (MS), ¹H-, ¹³C-NMR (nuclear magnetic resonance), heteronuclear single quantum coherence spectroscopy (HSQC) and heteronuclear multiple bond correlation (HMBC). The extracts, their sub-fractions and the isolated compounds exhibited promising antioxidant activities in vitro in DPPH and FRAP assays. Also, the extracts of P. alba leaf (PL), shoots (PS), and S. subserrata leaf (SL) demonstrated substantial antioxidant activities in vivo in the multicellular model organism Caenorhabditis elegans. For the first time, the isolated secondary metabolites, aromadendrin, tremuloidin, salicin, isorhamnetin-3-O-β-d-rutinoside, gallocatechin, triandrin, and chrysoeriol-7-O-glucuronide were investigated. They exhibited substantial antioxidant activities in vivo. Salicin, isorhamnetin-3-O-β-d-rutinoside and gallocatechin, in particular, protected the worms against a lethal dose of the pro-oxidant juglone (80 µM), decreased the endogenous reactive oxygen species (ROS) level to 45.34%, 47.31%, 68.09% and reduced juglone- induced hsp-16.2::GFP (green fluorescence protein) expression to 79.62%, 70.17%, 26.77%, respectively. However, only gallocatechin induced higher levels of sod-3 expression. These findings support the traditional use of Populus alba and Salix subserrata for treating inflammation especially when ROS are involved. Full article

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12 pages, 1601 KiB

Open AccessArticle

Evaluation of Phytochemical and Antioxidant Properties of 15 Italian Olea europaea L. Cultivar Leaves

by Francesca Nicolì, Carmine Negro, Marzia Vergine, Alessio Aprile, Eliana Nutricati, Erika Sabella, Antonio Miceli, Andrea Luvisi and Luigi De Bellis

Molecules 2019, 24(10), 1998; https://doi.org/10.3390/molecules24101998 - 24 May 2019

Cited by 54 | Viewed by 4399

Abstract

Olive leaf extracts are of special interest due to their proven therapeutic effects. However, they are still considered a by-product of the table olive and the oil industries. In order to learn possible ways of exploiting this waste for health purposes, we investigated [...] Read more.

Olive leaf extracts are of special interest due to their proven therapeutic effects. However, they are still considered a by-product of the table olive and the oil industries. In order to learn possible ways of exploiting this waste for health purposes, we investigated the phytochemical profiles and antioxidant activities in the leaves of 15 Italian Olea europaea L. cultivars grown in the same pedoclimatic conditions. The phenolic profiles and amounts of their seven representative compounds were analyzed using HPLC ESI/MS-TOF. The antioxidant activities were determined using three different antioxidant assays (DPPH, ORAC, and superoxide anion scavenging assay). Wide ranges of total phenolic content (11.39–48.62 g GAE kg⁻¹ dry weight) and antioxidant activities (DPPH values: 8.67–29.89 µmol TE mg⁻¹ dry weight, ORAC values: 0.81–4.25 µmol TE mg⁻¹ dry weight, superoxide anion scavenging activity values: 27.66–48.92 µmol TE mg⁻¹ dry weight) were found in the cultivars. In particular, the cultivars Itrana, Apollo, and Maurino, showed a high amount of total phenols and antioxidant activity, and therefore represent a suitable natural source of biological compounds for use in terms of health benefits. Full article

(This article belongs to the Special Issue Olive Bioactives: From Molecules to Human Health)

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