2. Academic Validation
  3. Quinoline-thiosemicarbazone-1,2,3-triazole-acetamide derivatives as new potent α-glucosidase inhibitors

Quinoline-thiosemicarbazone-1,2,3-triazole-acetamide derivatives as new potent α-glucosidase inhibitors

  • Sci Rep. 2024 Dec 28;14(1):30876. doi: 10.1038/s41598-024-81668-5.
Aynaz Khademian 1,  Mohammad Halimi 2,  Reza Azarbad 1,  Amir Hossein Alaedini 3,  Milad Noori 4,  Navid Dastyafteh 4,  Somayeh Mojtabavi 5,  Mohammad Ali Faramarzi 5,  Maryam Mohammadi-Khanaposhtani 6,  Mohammad Mahdavi 7
Affiliations

Affiliations

  • 1 Biomedical and Microbial Advanced Technologies (BMAT) Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
  • 2 Department of Biology, Islamic Azad University, Babol BranchBabol, Iran.
  • 3 School of Chemistry, College of Science, University of Tehran, Tehran, Iran.
  • 4 Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
  • 5 Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
  • 6 Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran. maryammoha@gmail.com.
  • 7 Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. momahdavi@tums.ac.ir.
PMID: 39730503 DOI: 10.1038/s41598-024-81668-5
Abstract

In this work, a novel series of quinoline-thiosemicarbazone-1,2,3-triazole-aceamide derivatives 10a-n as new potent α-glucosidase inhibitors was designed, synthesized, and evaluated. All the synthesized derivatives 10a-n were more potent than acarbose (positive control). Representatively, (E)-2-(4-(((3-((2-Carbamothioylhydrazineylidene)methyl)quinolin-2-yl)thio)methyl)-1H-1,2,3-triazol-1-yl)-N-phenethylacetamide (10n), as the most potent entry, with IC50 = 48.4 µM was 15.5-times more potent than acarbose. According to kinetic study, compound 10n was a competitive inhibitor against α-glucosidase. This compound formed the desired interactions with important residues of the binding pocket of α-glucosidase with favorable binding energy in the molecular docking and molecular dynamics. Compounds 10n, 10e, and 10 g as the most potent compounds among the synthesized compounds were evaluated in term of pharmacokinetics and toxicity via online servers. These evaluations predicted that compounds 10n, 10e, and 10 g had good pharmacokinetic properties and toxicity profile.

Keywords

1,2,3-Triazole; Quinoline; Thiosemicarbazone; α-Glucosidase inhibitors.

Figures
Products