Synthesis and QSAR analysis of oxazolo/thiazolo pyrimidine derivatives as potential antibacterial agents

Development of new antibacterial agents is increasingly important due to the resistance of microbes to the known antibacterial drugs. A series of benzylidene oxazolo/thiazolo (3,2-a)-pyrimidine-6- carboxamides were synthesized by condensing 2-oxo/thioxo-1,2,3,4-tetrahydropyrimidine carboxamides with various aromatic aldehydes. The structures of newly synthesized compounds were characterized by IR and NMR spectral data. All the compounds were screened for their antibacterial activity against Gram-positive and Gram-negative bacteria and MIC values were determined by serial dilution method. The 2D-QSAR studies were performed on VLife MDS software. QSAR equation revealed that selected physicochemical parameters such as Alignment Independent, Electrostatic and 2PathCount have correlation with antibacterial activity. Among synthesized benzylidene oxazolo or thiazolo (3,2-a) pyrimidine-6- carboxamide derivatives, compounds containing electron withdrawing polar group at para position of 5- phenyl ring and electron withdrawing non-polar group at para position of 2-benzylidene moiety of thiazolopyrimidine nucleus are better antibacterials.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Tyrosinase Inhibitory Activity, 3D QSAR, and Molecular Docking Study of 2,5-Disubstituted-1,3,4-Oxadiazoles

In continuation with our research program, in search of potent enzyme tyrosinase inhibitor, a series of synthesized 2,5-disubstituted 1,3,4-oxadiazoles have been evaluated for enzyme tyrosinase inhibitory activity. Subsequently, 3D QSAR and docking studies were performed to find optimum structural requirements for potent enzyme tyrosinase inhibitor from this series. The synthesized 20 compounds of 2,5-disubstituted-1,3,4-oxadiazole series were screened for mushroom tyrosinase inhibitory activity at various concentrations by enzyme inhibition assay. The percentage enzyme inhibition was calculated by recording absorbance at 492 nm with microplate reader. 3D QSAR and docking studies were performed using VLife MDS 3.5 software. In the series 2,5-disubstituted-1,3,4-oxadiazoles enzyme tyrosinase inhibitory activity was found to be dose dependent with maximum activity for compounds 4c, 4h, 4m, and 4r. 3D QSAR and docking studies revealed that more electropositive and less bulky substituents if placed on 1,3,4-oxadiazole nucleus may result in better tyrosinase inhibitory activity in the series

Targeting PPAR-gamma to design and synthesize antidiabetic thiazolidines

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