Targeting PPAR-gamma to design and synthesize antidiabetic thiazolidines
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Date
2018-06-27
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Abstract
A series of thiazolidine derivatives were designed by docking into PPAR-γ active site. The structure of target was
obtained from the protein data bank (PDB ID P37231). A library of 200 molecules was prepared on random basis.
Molecular docking studies were performed using VLife MDS 4.3 software. After molecular docking studies, the
4-substituted-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid N-[4-(2,4-dioxo-thiazolidin-5-
ylidenemethyl)-phenyl]-hydrazides (4a-4h) were selected for synthesis. The progress of reaction and purity of the
synthesized compounds were monitored by TLC and melting point. Structures of title compounds were confirmed
by elemental analysis, IR, 1H NMR and mass spectral data. The antidiabetic activity of title compounds was performed
using the Wistar rats by alloxan-induced method. The compounds have shown antidiabetic activity comparable
with the standard drug pioglitazone. These findings suggest that potent antidiabetics can be generated by
substituting nonpolar, electron withdrawing substituents at the fourth position of pyrimidine skeleton and hydrogen
bond acceptor at the nitrogen of the thiazolidine nucleus, to inhibit peroxisome proliferator-activated receptor-γ.
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Keywords
Alloxan, Antidiabetic, Docking, PPAR-γ, Thiazolidine