title: Design, synthesis and biological evaluation of novel coumarin thiazole derivatives as α-glucosidase inhibitors.
abstract: A new series of coumarin thiazole derivatives 7a-7t were synthesized, characterized by (1)H NMR, (13)C NMR and element analysis, evaluated for their α-glucosidase inhibitory activity. The majority of the screened compounds displayed potent inhibitory activities with IC50 values in the range of 6.24±0.07-81.69±0.39μM, when compared to the standard acarbose (IC50=43.26±0.19μM). Structure-activity relationship (SAR) studies suggest that the pattern of substitution in the phenyl ring is closely related to the biological activity of this class of compounds. Among all the tested molecules, compound 7e (IC50=6.24±0.07μM) was found to be the most active compound in the library of coumarin thiazole derivatives. Enzyme kinetic studies showed that compound 7e is a non-competitive inhibitor with a Ki of 6.86μM. Furthermore, the binding interactions of compound 7e with the active site of α-glucosidase were confirmed through molecular docking. This study has identified a new class of potent α-glucosidase inhibitors for further investigation.
authors.affiliation: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China. Electronic address: wanggch123@163.com.
authors.forename: Guangcheng
authors.initials: G
authors.lastname: Wang
authors.affiliation: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors.forename: Dianxiong
authors.initials: D
authors.lastname: He
authors.affiliation: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Peng
mesh_terms: D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D065089:Glycoside Hydrolase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology*; D000520:alpha-Glucosidases / Q000378:metabolism*
chemical_list: D003374:Coumarins; D065089:Glycoside Hydrolase Inhibitors; D013844:Thiazoles; C030123:coumarin; D000520:alpha-Glucosidases
keywords: Coumarin; Enzyme kinetic study; Molecular docking; Thiazole; α-Glucosidase inhibitor