Molecular modeling and synthesis of novel benzimidazole-derived thiazolidinone bearing chalcone derivatives: a promising approach to develop potential anti-diabetic agents

• Published in: ZEITSCHRIFT FUR NATURFORSCHUNG SECTION C-A JOURNAL OF BIOSCIENCES
• Main Authors: Abbasi, Shahzad Ahmad; Rehman, Wajid; Rahim, Fazal; Hussain, Rafaqat; Hawsawi, Mohammed B.; Alluhaibi, Mustafa S.; Alharbi, Majed; Taha, Muhammad; Khan, Shoaib; Rasheed, Liaqat; Wadood, Abdul; Ali Shah, Syed Adnan
• Format: Article; Early Access
• Language: English
• Published: WALTER DE GRUYTER GMBH 2024
• Subjects: Biochemistry & Molecular Biology; Pharmacology & Pharmacy
• Online Access: https://www-webofscience-com.uitm.idm.oclc.org/wos/woscc/full-record/WOS:001359237400001
• ISSN: 0939-5075; 1865-7125
• DOI: 10.1515/znc-2024-0202

Diabetes mellitus (DM) is a disorder which is raised at the alarming level and it is characterized by the hyperglycemia results from the impaired action of insulin, production of insulin or both of these simultaneously. Consequently, it causes problems or failure of different body organs such as kidneys, heart, eyes, nerve system. Since this disease cannot be completely cured until now, we aimed to design series of enzymes inhibitors and tested them for DM treatment. In this series, benzimidazole-based thiazolidinone bearing chalcone derivatives completed in a four step reaction and their structures were confirmed through various spectroscopic techniques. A significant efficacy on antidiabetic enzymes was observed, with IC50 values ranging from 25.05 +/- 0.04 to 56.08 +/- 0.07 mu M for alpha-amylase and 22.07 +/- 0.02 to 53.06 +/- 0.07 mu M for alpha-glucosidase. The obtained results were compared to those of the standard glimepiride drug (IC50 = 18.05 +/- 0.07 mu M for alpha-amylase and IC50 = 15.02 +/- 0 .03 mu M for alpha-glucosidase). The synthesized compounds showed promising antidiabetic potency. Moreover, a molecular docking study was conducted on the most active analogs of the compounds to better understand their interactions with the active sites of the targeted enzymes.