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Diabetes Mellitus (DM) is linked to various factors causing cardiovascular diseases, with uncontrolled postprandial hyperglycemia being a direct contributor. α‐Glucosidase inhibitors (AGIs) aid in reducing postprandial hyperglycemia, potentially mitigating cardiovascular risks. In order to synthesize novel chemical scaffolds with possible α‐glucosidase inhibition activity, a series of novel soritin sulfonamide derivatives were synthesized. The soritin hydrazide was treated with various aryl sulfonyl chlorides to obtain targeted compounds (1–16). Findings suggested that all compounds have better α‐glucosidase inhibition compared to standard drugs, acarbose (2187.00 ± 1.25 μM) and 1‐deoxynojirimycin (334.90 ± 1.10 μM), with IC50 values ranging from 3.81 ± 1.67 μM to 265.40 ± 1.58 μM. The most potent analog was Compound 13, a trichloro phenyl substituted compound, with IC50 value of 3.81 ± 1.67 μM. Structure–activity relationship (SAR) showed that introducing an additional chlorine group into the parent nucleus increases the potency. The docking studies validated that Compound 13 established hydrogen bonds with the active site residues Asp214, Glu276, and Asp349, while being further stabilized by hydrophobic interactions, providing an explanation for its high potency. [ABSTRACT FROM AUTHOR]

The chemical compositions, in vitro and in silico anti-dengue activity of the essential oils of the rhizomes of Curcuma longa Linn., C. aeruginosa Roxb., and C. xanthorrhiza Roxb. had been investigated. The C. longa oil was mainly composed of ar-turmerone (54.0%) and curlone (17.7%), while the C. aeruginosa oil was rich in curzerenone (23.4%), 1,8-cineole (21.2%), and camphor (7.1%). Xanthorrhizol (21.6%), β-curcumene (19.5%), ar-curcumene (14.2%), and camphor (9.2%) were the major compounds in the C. xanthorrhiza oil. Among the oils, the C. longa oil was found to be the most active NSB-NS3 protease inhibitor (IC50 1.98 μg/mL). PLS biplot disclosed that the essential oils were classified into three separated clusters based on their characteristic chemical compositions, with C. longa positioned closest to the in vitro anti-dengue activity. Four compounds from the C. longa oil have both hydrogen and hydrophobic bonds that could be responsible for the DENV-2 NS2B-NS3 inhibitory effect. [ABSTRACT FROM AUTHOR]

CYP3A4 is a major hepatic enzyme essential for metabolizing diverse chemical entities. The development of CYP3A4 substrate and inhibitor classifier models is a valuable research strategy to prevent toxicokinetics. Currently, no molecular docking model is available to classify the substrates and inhibitors for a wide range of chemical entities. This study generated a CYP3A4 substrate-inhibitor classifier model using multivariate analysis of selected variables from site of metabolism (SOM)-based docking results and molecular descriptors. CYP3A4 SOM-based molecular docking experiment was performed on the substrates and inhibitors from the DrugBank database. The relevant descriptors were selected using the area under the receiving operating curve (AUROC) and boxplot analysis. The selected variables were used to generate a CYP3A4 substrate-inhibitor classifier model using multivariate analysis. Two complexes were selected for molecular dynamic simulations. A total of 326 substrates and 154 inhibitors were successfully docked. The SOM-based docking model predicted 78.5% SOM correctly of the substrates. The CDOCKER energy, improper dihedral energy, potential energy, initial RMS (root mean square) gradient, and RMS gradient demonstrated acceptable AUROC, sensitivity, specificity, and Youden's index results. The selected variables were subjected to multivariate analysis, and the PLS-DA analysis classification model showed promising performance in predicting chemical entities' behavior as substrates or inhibitors. This model classified the external samples correctly with over 70.0% prediction accuracy. Molecular dynamic simulations showed that the selected complexes obtained from the docking model produced stable complexes. The classifier model is applicable as a research tool for the early stages of drug discovery. In silico structure-based analysis of new chemical entities toward CYP3A4 metabolism and inhibitory activity is helpful in pharmacokinetic research. This study analysed the results of SOM-based molecular docking and relevant descriptors using multivariate analysis to generate CYP3A4 substrate-inhibitor classifier model. [ABSTRACT FROM AUTHOR]

Introduction: Ficus deltoidea Jack (Moraceae) is a plant used in Malaysia to treat various ailments, including diabetes. The presence of several varieties raises essential questions regarding which is the potential bioactive variety and what are the bioactive metabolites. Objectives: Here, we explored the phytochemical diversity of the seven varieties from Peninsular Malaysia using Nuclear Magnetic Resonance (NMR) and Liquid Chromatography–Mass Spectrometry (LC–MS) analyses and correlated it with the α‐glucosidase inhibitory activity. Methodology: The Nuclear Overhauser Effect Spectroscopy (NOESY) One‐Dimensional (1D)‐NMR and LC–MS data were processed, annotated, and correlated with in vitro α‐glucosidase inhibitory using multivariate data analysis. Results: The α‐glucosidase results demonstrated that different varieties have varying inhibitory effects, with the highest inhibition rate being F. deltoidea var. trengganuensis and var. kunstleri. Furthermore, diverse habitats and plant ages could also influence the inhibitory rate. The heat map from NMR and LC–MS profiles showed unique patterns according to varying levels of α‐glucosidase inhibition rate. The Partial Least Squares (PLS) model constructed from both NMR and LC–MS further confirmed the correlation between the α‐glucosidase inhibition rate of F. deltoidea varieties and its metabolite profiles. The Variable Influence on Projection (VIP) and correlation coefficient (p(corr)) values values were used to determine the highly relevant metabolites for explaining the anticipated inhibitory action. Conclusion: NMR and LC–MS annotations allow the identification of flavan‐3‐ols and proanthocyanidins as the key bioactive factors. Our current results demonstrated the value of multivariate data analysis to predict the quality of herbal materials from both biological and chemical aspects. Ficus deltoidea is used in Malaysia to treat various ailments, including diabetes. We explored the phytochemical diversity of seven Peninsular Malaysian varieties and correlated it with the α‐glucosidase inhibitory potential. Partial least squares (PLS) correlation models constructed from NMR and LC‐MS data with α‐glucosidase inhibitory rate predicted var. trengganuensis and var. kunstleri as the bioactive varieties, with proanthocyanidins and flavan‐3‐ols identified as the key bioactive factors. [ABSTRACT FROM AUTHOR]

Eleven compounds: goniomicin A (1), goniomicin B (2), goniomicin C (3), goniomicin D (4), tapisoidin (5), goniothalamin (6), 9-deoxygoniopypyrone (7), pterodondiol (8), liriodenine (9), benzamide (10) and cinnamic acid (11), were isolated from the stem bark of Goniothalamus tapisoides. All compounds were identified by spectroscopic analysis and, for known compounds, by comparison with published data. Goniothalamin (6) exhibited mild cytotoxic activity towards a colon cancer cell line (HT-29), with an IC50 value of 64.17 ± 5.60 μM. Goniomicin B (2) give the highest antioxidant activity in the DPPH assay among all compounds tested, with an IC50 of 0.207 μM. [ABSTRACT FROM AUTHOR]

Introduction: Swietenia macrophylla King (family Meliaceae) is a timber species with medicinal value. The seed is used as traditional medicine, however there are reports of liver injury, suspected to be associated with S. macrophylla seed consumption. The aim of this study is to assess the toxicity of S. macrophylla seed prepared in different solvent of extraction using a cell-based assay. Methods: Two methods were employed in the preparation of the seed extracts. In the first method, the dried seed was extracted with ethanol, methanol, or 50% ethanol. In the second method, the dried seed was extracted sequentially with solvents following ascending polarity. HepG2 cells were used as an in vitro liver model. The cells were treated with various concentrations of seed extracts and the cell viability was assessed by the 3, (4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay. Results: Swietenia macrophylla seed was cytotoxic towards HepG2 cells with the chloroform extract being the most cytotoxic, followed by the ethyl acetate and hexane extracts. The ethanol, methanol, and 50% ethanol extracts were also cytotoxic but to a lesser extent than the three non-polar extracts. The water extract does not negatively affect cell viability. Conclusion: The findings reveal the cytotoxic effect of S. macrophylla seed is dependent on solvent extraction. [ABSTRACT FROM AUTHOR]

Introduction: Ficus deltoidea Jack (Moraceae) is a plant used in Malaysia to treat various ailments, including diabetes. The presence of several varieties raises essential questions regarding which is the potential bioactive variety and what are the bioactive metabolites., Objectives: Here, we explored the phytochemical diversity of the seven varieties from Peninsular Malaysia using Nuclear Magnetic Resonance (NMR) and Liquid Chromatography-Mass Spectrometry (LC-MS) analyses and correlated it with the α-glucosidase inhibitory activity., Methodology: The Nuclear Overhauser Effect Spectroscopy (NOESY) One-Dimensional (1D)-NMR and LC-MS data were processed, annotated, and correlated with in vitro α-glucosidase inhibitory using multivariate data analysis., Results: The α-glucosidase results demonstrated that different varieties have varying inhibitory effects, with the highest inhibition rate being F. deltoidea var. trengganuensis and var. kunstleri. Furthermore, diverse habitats and plant ages could also influence the inhibitory rate. The heat map from NMR and LC-MS profiles showed unique patterns according to varying levels of α-glucosidase inhibition rate. The Partial Least Squares (PLS) model constructed from both NMR and LC-MS further confirmed the correlation between the α-glucosidase inhibition rate of F. deltoidea varieties and its metabolite profiles. The Variable Influence on Projection (VIP) and correlation coefficient (p(corr)) values values were used to determine the highly relevant metabolites for explaining the anticipated inhibitory action., Conclusion: NMR and LC-MS annotations allow the identification of flavan-3-ols and proanthocyanidins as the key bioactive factors. Our current results demonstrated the value of multivariate data analysis to predict the quality of herbal materials from both biological and chemical aspects., (© 2022 John Wiley & Sons Ltd.)

Eleven compounds:goniomicin A (1), goniomicin B (2), goniomicin C (3), goniomicin D (4), tapisoidin (5), goniothalamin (6), 9-deoxygoniopypyrone (7), pterodondiol (8), liriodenine (9), benzamide (10) and cinnamic acid (11), were isolated from the stem bark of Goniothalamus tapisoides. All compounds were identified by spectroscopic analysis and, for known compounds, by comparison with published data. Goniothalamin (6) exhibited mild cytotoxic activity towards a colon cancer cell line (HT-29), with an IC(50)value of 64.17 ± 5.60 µM. Goniomicin B (2) give the highest antioxidant activity in the DPPH assay among all compounds tested, with an IC(50) of 0.207 µM.