Synthesis and biological evaluation of 1,6-bis-triazole-2,3,4-tri-O-benzyl-α-d-glucopyranosides as a novel α-glucosidase inhibitor in the treatment of Type 2 diabetes

• Published in: Bioorganic & medicinal chemistry letters Vol. 50; p. 128331
• Main Authors: Chaidam, Suksamran, Saehlim, Natthiya, Athipornchai, Anan, Sirion, Uthaiwan, Saeeng, Rungnapha
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 15.10.2021; Elsevier
• Subjects: alpha-Glucosidases - chemistry; alpha-Glucosidases - metabolism; Bis-triazole glucoside; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Diabetes Mellitus, Type 2 - drug therapy; Glucans - pharmacology; Glycoside Hydrolase Inhibitors - pharmacology; Humans; Hypoglycemic Agents - chemical synthesis; Hypoglycemic Agents - pharmacology; Life Sciences & Biomedicine; Models, Molecular; Molecular Docking Simulation; Molecular Structure; Pharmacology & Pharmacy; Physical Sciences; Protein Binding; Protein Conformation; Science & Technology; Sugar; Type 2 diabetes mellitus; α-glucosidase inhibitor; Bis-triazole glucoside; Type 2 diabetes mellitus; α-glucosidase inhibitor; Sugar; IN-VITRO; MANAGEMENT; alpha-glucosidase inhibitor; CLICK CHEMISTRY; 1,2,3-TRIAZOLES; MELLITUS
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2021.128331

[Display omitted] •A novel series of 1,6-bis-triazole-benzyl-α-glucoside derivatives (7a-7ee) were designed and synthesized through simple, effective methods, all high yielding.•All compounds were evaluated for in vitro α-glucosidase inhibitory activity.•Compound 7dd showed excellent activity with IC50 values of 3.73 ± 0.05 µM or around 39 times that of the standard drug acarbose.•Computational studies suggest potent compounds 7f, 7z, 7cc and 7dd possess good binding energy and bind well in the active site of α-glucosidase. A novel series of 1,6-bis-triazole-benzyl-α-glucoside derivatives (7a-7ee) were designed, synthesized and evaluated for inhibitory activity against α-glucosidase. Most of the synthesized compounds exhibited good activity with IC50 ranging from 3.73 µM to 53.34 µM and are more potent than the standard drug acarbose (IC50 = 146.25 ± 0.40 µM). SARs study showed the ester and menthol moiety play an important role in the inhibitory activity. The molecular docking model of the potent compounds 7f, 7z, 7cc and 7dd showed good binding energy and interacts well with amino acid residues around the active site of the enzyme, which confirmed the in vitro activity results.