title: Synthesis, in vitro evaluation and molecular docking studies of novel amide linked triazolyl glycoconjugates as new inhibitors of α-glucosidase.
abstract: A series of N-substituted amide linked triazolyl β-d-glucopyranoside derivatives (4a-l) were synthesized and their in vitro inhibitory activity against yeast α-glucosidase enzyme [EC.3.2.1.20] was assessed. Compounds 4e (IC50=156.06μM), 4f (IC50=147.94μM), 4k (IC50=127.71μM) and 4l (IC50=121.33μM) were identified as the most potent inhibitors for α-glucosidase as compared to acarbose (IC50=130.98μM) under the same in vitro experimental conditions. Kinetic study showed that both 4e and 4f inhibit the enzyme in a competitive manner with p-nitrophenyl α-d-glucopyranoside as substrate. Molecular docking studies of 4e, 4f, 4k and 4l were also carried out using homology model of α-glucosidase to find out the binding modes responsible for the inhibitory activity. This study revealed that the binding affinity of compounds 4e, 4f, 4k and 4l for α-glucosidase were -8.2, -8.6, -8.3 and -8.5kcal/mol respectively, compared to that of acarbose (-8.9kcal/mol). The results suggest that the N-substituted amide linked triazole glycoconjugates can reasonably mimic the substrates for the yeast α-glucosidase.
authors.affiliation: Department of Organic and Medicinal Chemistry, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, India.
authors.forename: Shyam Ji
authors.initials: SJ
authors.lastname: Gupta
authors.affiliation: Department of Organic and Medicinal Chemistry, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, India.
authors.forename: Samrat
authors.initials: S
authors.lastname: Dutta
authors.affiliation: Department of Organic and Medicinal Chemistry, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, India.
authors.forename: Rahul L
authors.initials: RL
authors.lastname: Gajbhiye
authors.affiliation: Department of Organic and Medicinal Chemistry, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, India.
authors.forename: Parasuraman
authors.initials: P
authors.lastname: Jaisankar
authors.affiliation: Department of Organic and Medicinal Chemistry, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, India. Electronic address: aksen@iicb.res.in.
authors.forename: Asish Kumar
authors.initials: AK
authors.lastname: Sen
mesh_terms: D000577:Amides / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006001:Glycoconjugates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D065089:Glycoside Hydrolase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D000520:alpha-Glucosidases / Q000378:metabolism*
chemical_list: D000577:Amides; D006001:Glycoconjugates; D065089:Glycoside Hydrolase Inhibitors; D000520:alpha-Glucosidases
keywords: Amide linked glucopyranoside; Diabetes; Docking studies; Glycoconjugate; Triazole; α-Glucosidase