Synthesis, molecular docking study, MD simulation, ADMET, and drug likeness of new thiazolo[3,2-a]pyridine-6,8-dicarbonitrile derivatives as potential anti-diabetic agents.

Autor: Aghahosseini F; Department of Chemistry, Faculty of Science, Imam Khomeini International University, Qazvin, Iran., Bayat M; Department of Chemistry, Faculty of Science, Imam Khomeini International University, Qazvin, Iran., Sadeghian Z; Department of Chemistry, Faculty of Science, Imam Khomeini International University, Qazvin, Iran., Gheidari D; Department of Chemistry, Faculty of Science, University of Guilan, Rasht, Iran., Safari F; Department of Chemistry, Faculty of Science, University of Guilan, Rasht, Iran.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Sep 12; Vol. 19 (9), pp. e0306973. Date of Electronic Publication: 2024 Sep 12 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0306973
Abstrakt: There are numerous uses for the pharmacological effects of thiazolo-pyridine and its derivatives. The main objective of the study was to synthesis 10 novel derivatives of thiazolo[3,2-a] pyridine-6,8-dicarbonitrile with a 22-78% yield, with a focus on their potential anti-diabetic properties. We investigated the interactions between these compounds and the enzyme α-amylase through an in silico study involving molecular docking. According to the docking analysis results, the resulting compounds had advantageous inhibitory properties. With a docking score of -7.43 kcal/mol against the target protein, compound 4e performed best. The stability root-mean-square deviation (RMSD) showed that the complex stabilizes after 25 ns and with minor perturbation at 80. The RMSF values of the ligand-protein complex indicate that the following residues have interacted with compound 4e during the MD simulation: Trp58, Trp59, Tyr62, Gln63, His101, Val107, lle148, Asn152, Leu162, Thr163, Gly164, Leu165, Asp197, Ala198, Asp 236, Leu237, His299, Asp300, and His305. Moreover, the pharmacokinetic and drug-like properties of the synthesized derivatives of 2-arylamino-dihydroindeno[1,2-b] pyrrol-4(1H)-one suggest that they have the potential to be effective inhibitors of α-amylase and should be considered for further research. Nevertheless, it is crucial to ascertain the in vivo and in vitro effectiveness of these compounds through biochemical and structural investigations.
Competing Interests: NO authors have competing interests.
(Copyright: © 2024 Aghahosseini et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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