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

Suksamran Chaidam; Natthiya Saehlim; Anan Athipornchai; Uthaiwan Sirion; Rungnapha Saeeng

doi:10.1016/j.bmcl.2021.128331

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

Bioorg Med Chem Lett. 2021 Oct 15:50:128331. doi: 10.1016/j.bmcl.2021.128331. Epub 2021 Aug 19.

Authors

Suksamran Chaidam¹, Natthiya Saehlim¹, Anan Athipornchai², Uthaiwan Sirion², Rungnapha Saeeng³

Affiliations

¹ Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Burapha University, Sangesook, ChonBuri 20131, Thailand.
² Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Burapha University, Sangesook, ChonBuri 20131, Thailand; The Research Unit in Synthetic Compounds and Synthetic Analogues from Natural Product for Drug Discovery (RSND), Burapha University, Chonburi 20131, Thailand.
³ Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Burapha University, Sangesook, ChonBuri 20131, Thailand; The Research Unit in Synthetic Compounds and Synthetic Analogues from Natural Product for Drug Discovery (RSND), Burapha University, Chonburi 20131, Thailand. Electronic address: rungnaph@buu.ac.th.

PMID: 34418573
DOI: 10.1016/j.bmcl.2021.128331

Abstract

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.

Keywords: Bis-triazole glucoside; Sugar; Type 2 diabetes mellitus; α-glucosidase inhibitor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Diabetes Mellitus, Type 2 / drug therapy*
Glucans / pharmacology*
Glycoside Hydrolase Inhibitors / pharmacology*
Humans
Hypoglycemic Agents / chemical synthesis*
Hypoglycemic Agents / pharmacology*
Models, Molecular
Molecular Docking Simulation
Molecular Structure
Protein Binding
Protein Conformation
alpha-Glucosidases / chemistry
alpha-Glucosidases / metabolism

Substances

Glucans
Glycoside Hydrolase Inhibitors
Hypoglycemic Agents
alpha-Glucosidases