Structure-Activity Design, Synthesis and Biological Activity of Newer Imidazole- Triazine Clubbed Derivatives as Antimicrobial and Antitubercular Agents

Abstract

Background: Imidazole and triazine derivatives act as antimicrobial and antitubercular agents. 2D-QSAR determination estimates the pharmacological activity based on the thermodynamic properties of the structure. Objective: The structural arrangements and thermodynamic properties of the imidazole derivatives are necessary for the enhancement of pharmacological activity. So,imidazole-triazine clubbed derivatives were designed based on molecular modeling 2D-QSAR study on antitubercular activity. Methods: PLSR method is applied for 2D-QSAR determination of the (Z)-5-ethylidene-3-(4- methoxy-6-methyl-1,3,5-triazin-2-yl)-2-phenyl-3,5-dihydro-4H-imidazol-4-one (B1-B10). The designed compounds were synthesized and spectrally evicted by IR, 1H NMR, 13C NMR, and mass spectra data as well as biologically screened against the different antitubercular and antimicrobial species. Result: Compounds B4, B6, and B7 were found potent against the different antimicrobial species. Compound B3 was more effective against the M. tuberculosis H37Rv. Statistically significant QSAR model generated by PLSR methods showed external r2=0.9775 and internal q2=0.2798 predictive abilities. Furthermore, the model also incorporated three parameters, Polar Surface Area Excluding Pand S, Mom Inertia Y, and SsCH3 count, with their corresponding values for each molecule. Conclusion: The 2D-QSAR study revealed that antitubercular activity was directly proportional to the total surface area of the polar atoms having molecules and the moment of inertia on the Y-axis. At the same time, antitubercular activity was inversely proportional to the methyl group joined with a single bond. The present study afforded favorable results, which were further used to generate lead target molecules.