Synthesis, Characterization, Antitubercular Activity and Docking Studies of 2-(benzo [d]oxazol-2-ylthio)-1-(3-(4-fluoro-3- methylphenyl)-5-(substituted aryl)-4,5-dihydro-1H-pyrazol-1-yl) ethanone

A new series of 2-(benzo[d]oxazol-2-ylthio)-1-(3-(4-fluoro-3-methylphenyl)-5- (substituted aryl)-4,5-dihydro-1H-pyrazol-1-yl)ethanone (6a-6j) were designed and synthesized from the intermediate chalcones (1a-1j). The synthesized compounds were characterized by FT-IR, 1 H-NMR, Mass spectroscopy and bases of elemental analysis. The agar dilution method (In vitro M. tuberculosis method) was employed for anti-tubercular screening. From the study, it was revealed that compounds 6b and 6h showed increased potency. In phenyl ring attached to 4,5-dihydropyrazole ring presence of electron donating substituent like dimethylamino, hydroxy and methoxy moiety mightbe responsible for the powerful anti-mycobacterial activity displayed by derivatives 6b and 6h. Further docking studies were performed to predict the interactions of the target compounds 6a-6j within the Mycobacterium tuberculosis enoyl reductase enzyme by their scores and mode of binding to amino acids. In addition, drug-likeness score and molecular properties responsible for a good pharmacokinetic profile were calculated by Osiris property explorer and Molinspiration online toolkit, respectively. From the results, it was revealed that the synthesized compounds with electron releasing groups showed the most potent activity compared to that of standard drug.