Design, Drug-Likeness, Synthesis, Characterization, Antimicrobial Activity, Molecular Docking, and MTT Assessment of 1,3-Thiazolidin-4-one Bearing Piperonal and Pyrimidine Moieties

Abstract

The recent study reported the designing of substituted 3-[4-(1,3-benzodioxol-5-yl)-6-(pyridin-2-yl)pyrimidin-2-yl]-2-(pyridin-2-yl)-1,3-thiazolidin-4-one derivatives and assessed computationally to calculate the bioactivity and physicochemical properties. The substituted 3-[4-(1,3-benzodioxol-5-yl)-6-(pyridin-2-yl)pyrimidin-2-yl]-2-(pyridin-2-yl)-1,3-thiazolidin-4-one derivatives represented the bioactivity score in the zone for an active drug molecule and were in compliance with the Lipinski Rule of five. Then the synthesis, characterization, and biological screening as antimicrobial potential and percent viability of cells were carried out for the substituted 3-[4-(1,3-benzodioxol-5-yl)-6-(pyridin-2-yl)pyrimidin-2-yl]-2-(pyridin-2-yl)-1,3-thiazolidin-4-one derivatives. The zone of inhibition and minimum inhibitory concentration (MIC) findings portrayed that the compounds-(IV) and compound-(V) possessed better antimicrobial activity than the reference drug ciprofloxacin, while the significant antimicrobial potential was observed by other members of the series. The molecular docking studies were performed to assist the in vitro antimicrobial results and the findings exhibited that significant H-bonding in between the substituted 3-[4-(1,3-benzodioxol-5-yl)-6-(pyridin-2-yl)pyrimidin-2-yl]-2-(pyridin-2-yl)-1,3-thiazolidin-4-one derivatives and the residues of GlcN-6-P-synthase, like ASP 474 (I–IX), SER 316 (I–VI), ASN 522 (I–IX), TRP 313 (V) with good binding affinity ranging –7.7 to –6.8 kcal/mole. The compounds represented the less toxic effects to the HepG2 cells and the percent viability of the cells ranging from 93–98%, 73–78% and 70–76% up to 3.125, 50 , 100 mmol/L respectively.