In Silico (3D-QSAR) Designed, Study, Synthesis and Anti-tubercular Evaluation of Pyrazolo-Pyrimidine Derivatives

Abstract

Background: A 3D-QSAR study based on CoMFA and CoMSIA was performed on these pyrazole-pyrimidine derivatives to correlate their chemical structures with the observed activity against M. tuberculosis. Objective: The current research aimed to synthesize and evaluateed pyrazole-pyrimidine based antitubercular agents by an in vitro microbial study based on our previously reported 3D-QSAR. Methods: The designed molecules were synthesised via chalcone intermediate and cyclisation using guanidine and urea. The molecules were then characterized by various spectroscopic methods like IR, MASS, 1H-NMR, 13C-NMR and in vitro evaluation against M. tuberculosis H37Rv. They were further evaluated under anaerobic condition and their intracellular assay was studied. The compounds were further examined for cytotoxicity towards eukaryotic cells. Results: Compounds 3a, 3c and 3i were found to be the most effective against M. tuberculosis H37Rv, with IC50 of 16μM, 13μM and 15μM, respectively. Conclusion: The designed strategy, to enhance the antitubercular activity against M. tuberculosis H37Rv, was proved fruitful. On considering the overall data, the promising results would be useful to design the next target with improved efficacy and potency of compounds for further medicinal importance.