Background:
Imidazole and triazine derivatives act as antimicrobial and antitubercular agents. 2D-QSAR determination estimates the pharmacological activity on the basis of 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 on the bases of molecular modeling 2D-QSAR study of antitubercular activity.
Methods:
PLSR method was 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, Mass spectra data as well as biologically screened opposite different antitubercular and antimicrobial species.
Result:
Compounds B4, B6, B7 were founds potent against different antimicrobial species. Compound B3 was more effective against M. tuberculosis H37Rv. Statistically significant QSAR model generated by PLSR methods shows external r2=0.9775 and internal q2=0.2798 predictive ability. Whereas, the model incorporates with three parameters PolarSurfaceAreaExcluding P and S, MomInertiaY and SsCH3count with their corresponding values for each molecule.
Conclusion:
2D-QSAR study advised antitubercular activity directly proportional to total surface area of the polar atoms having molecules and moment of inertia on Y-axis. Whereas, inversely proportional to methyl group joined with single bond. The present study afforded favorable results which were further used to generate lead target molecules.