1. Synthesis of thiazolidine-2,4-dione tethered 1,2,3-triazoles as α-amylase inhibitors: In vitro approach coupled with QSAR, molecular docking, molecular dynamics and ADMET studies.
- Author
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Singh R, Sindhu J, Devi M, Kumar P, Lal S, Kumar A, Singh D, and Kumar H
- Subjects
- Molecular Structure, Dose-Response Relationship, Drug, Humans, Triazoles chemistry, Triazoles pharmacology, Triazoles chemical synthesis, Molecular Docking Simulation, alpha-Amylases antagonists & inhibitors, alpha-Amylases metabolism, Molecular Dynamics Simulation, Quantitative Structure-Activity Relationship, Thiazolidinediones chemistry, Thiazolidinediones chemical synthesis, Thiazolidinediones pharmacology
- Abstract
A new series of thiazolidine-2,4-dione tethered 1,2,3-triazole derivatives were designed, synthesized and screened for their α-amylase inhibitory potential employing in vitro and in silico approaches. The target compounds were synthesized with the help of Cu (I) catalyzed [3 + 2] cycloaddition of terminal alkyne with numerous azides, followed by unambiguously characterizing the structure by employing various spectroscopic approaches. The synthesized derivatives were assessed for their in vitro α-amylase inhibition and it was found that thiazolidine-2,4-dione derivatives 6e, 6j, 6o, 6u and 6x exhibited comparable inhibition with the standard drug acarbose. The compound 6e with a 7-chloroquinolinyl substituent on the triazole ring exhibited significant inhibition potential with IC
50 value of 0.040 μmol mL-1 whereas compound 6c (IC50 = 0.099 μmol mL-1 ) and 6h (IC50 = 0.098 μmol mL-1 ) were poor inhibitors. QSAR studies revealed the positively correlating descriptors that aid in the design of novel compounds. Molecular docking was performed to investigate the binding interactions with the active site of the biological receptor and the stability of the complex over a period of 100 ns was examined using molecular dynamics studies. The physiochemical properties and drug-likeliness behavior of the potent derivatives were investigated by carrying out the ADMET studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)- Published
- 2024
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