ABSTRACT
A novel series of chromone-isatin derivatives 6a-6p were designed, synthesized and characterized by 1H NMR, 13C NMR and HRMS. These novel synthetic compounds were evaluated for inhibitory activity against yeast α-glucosidase enzyme. The results of biological test have shown that all tested compounds exhibited excellent to potent inhibitory activity in the range of IC50â¯=â¯3.18⯱â¯0.12-16.59⯱â¯0.17⯵M as compared to the standard drug acarbose (IC50â¯=â¯817.38⯱â¯6.27⯵M). Compound 6j (IC50â¯=â¯3.18⯱â¯0.12⯵M) with a hydroxyl group at the 7-position of chromone and a 4-bromobenzyl group at the N1-positions of isatin, was found to be the most active compound among the series. Furthermore, molecular docking study was performed to help understand binding interactions of the most active analogs with α-glucosidase enzyme. These results indicated that this class of compounds had potential for the development of anti-diabetic agents.
Subject(s)
Chromones/pharmacology , Glycoside Hydrolase Inhibitors/pharmacology , Isatin/pharmacology , Molecular Docking Simulation , alpha-Glucosidases/metabolism , Chromones/chemistry , Dose-Response Relationship, Drug , Glycoside Hydrolase Inhibitors/chemical synthesis , Glycoside Hydrolase Inhibitors/chemistry , Isatin/chemistry , Molecular Structure , Saccharomyces cerevisiae/enzymology , Structure-Activity RelationshipABSTRACT
A series of chalcones containing naphthalene moiety 4a-4p have been synthesized, characterized by 1H NMR and 13C NMR and evaluated for their in vitro anticancer activity. The majority of the screened compounds displayed potent anticancer activity against both HCT116 and HepG2 human cancer cell lines. Among the series, compound 4h with a diethylamino group at the para position of the phenyl ring exhibited the most potent anticancer activity against HCT116 and HepG2 cell lines with IC50 values of 1.20⯱â¯0.07 and 1.02⯱â¯0.04⯵M, respectively. The preliminary structure-activity relationship has been summarized. Tubulin polymerization experiments indicated that 4h effectively inhibited tubulin polymerization and flow cytometric assay revealed that 4h arrests HepG2 cells at the G2/M phase in a dose-dependent manner. Furthermore, molecular docking studies suggested that 4h binds to the colchicine binding site of tubulin.
Subject(s)
Antineoplastic Agents/pharmacology , Chalcones/pharmacology , Naphthalenes/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/metabolism , Binding Sites , Cell Line, Tumor , Chalcones/chemical synthesis , Chalcones/chemistry , Chalcones/metabolism , Drug Screening Assays, Antitumor , G2 Phase Cell Cycle Checkpoints/drug effects , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Molecular Structure , Naphthalenes/chemical synthesis , Naphthalenes/chemistry , Naphthalenes/metabolism , Protein Binding , Structure-Activity Relationship , Tubulin/chemistry , Tubulin/metabolism , Tubulin Modulators/chemical synthesis , Tubulin Modulators/chemistry , Tubulin Modulators/metabolism , Tubulin Modulators/pharmacologyABSTRACT
Benzothiazole-triazole derivatives 6a-6s have been synthesized and characterized by ¹HNMR and 13C-NMR. All synthetic compounds were screened for their in vitro α-glucosidase inhibitory activity by using Baker's yeast α-glucosidase enzyme. The majority of compounds exhibited a varying degree of α-glucosidase inhibitory activity with IC50 values between 20.7 and 61.1 µM when compared with standard acarbose (IC50 = 817.38 µM). Among the series, compound 6s (IC50 = 20.7 µM) bearing a chlorine group at the 5-position of the benzothiazole ring and a tertbutyl group at the para position of the phenyl ring, was found to be the most active compound. Preliminary structure-activity relationships were established. Molecular docking studies were performed to predict the binding interaction of the compounds in the binding pocket of the enzyme.
