Journal Article

Introduction of new quinolone-2-thio-acetamide-propane hydrazide-benzimidazole derivatives as new α-glucosidase and α-amylase inhibitors

Safapoor, Sajedeh, Taslimi, Parham, Mahdavi, Mohammad, Mohammadi-Khanaposhtani, Maryam, Larijani, Bagher, Noori, Milad, Nikfar, Parisa, Dastyafteh, Navid, Ghafouri, Seyedeh Niloufar, Karimian, Somaye

2025

Overview

In the present work, new quinolone-2-thio-acetamide-propane hydrazide-benzimidazole derivatives 12a-o were assigned as potent anti-diabetic agents that targeting α-glucosidase and α-amylase as two important targets in treatment of type 2 diabetes. General scaffold of these compounds was designed based on the reported potent α-glucosidase and α-amylase inhibitors and derivation was performed in acetamide moiety. In vitro evaluation of the new compounds 12a-o demonstrated that most of the synthesized compounds were more potent than standard inhibitor acarbose against α-glucosidase while all these new compounds were more potent than acaerbose against α-amylase. The most potent compound against both studied enzymes was compound 12n that was a 4-fluorophenylacetamide derivative. This compound was 5 and 23.8 folds more potent than acarbose against α-glucosidase and α-amylase, respectively, and with excellent binding energies in comparison to acarbose attached to active sites of these enzymes. Molecular dynamics and pharmacokinetic studies of compound 12n was also performed.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/154 / 631/45 / Acarbose / alpha-Amylases - antagonists & inhibitors / alpha-Amylases - chemistry / alpha-Glucosidases - chemistry / alpha-Glucosidases - metabolism / Animals / Benzimidazole / Benzimidazoles / Benzimidazoles - chemical synthesis / Benzimidazoles - chemistry / Benzimidazoles - pharmacokinetics / Benzimidazoles - pharmacology / Biological activity / Diabetes / Diabetes mellitus (non-insulin dependent) / Diabetes Mellitus, Type 2 - drug therapy / Enzymes / Glycoside Hydrolase Inhibitors - chemical synthesis / Glycoside Hydrolase Inhibitors - chemistry / Glycoside Hydrolase Inhibitors - pharmacokinetics / Glycoside Hydrolase Inhibitors - pharmacology / Humanities and Social Sciences / Humans / Hypoglycemic Agents - chemical synthesis / Hypoglycemic Agents - chemistry / Hypoglycemic Agents - pharmacology / Insulin / Metabolism / Molecular Docking Simulation / Molecular dynamics / Molecular Dynamics Simulation / multidisciplinary / Pharmacokinetics / Propane / Propane hydrazide / Quinolone-2-thio-acetamide / Quinolones / Quinolones - chemistry / Quinolones - pharmacology / Science / Science (multidisciplinary) / Structure-Activity Relationship / Α-Amylase / Α-Glucosidase