Abstract

DESIGNING OF NOVEL CINNAMOYL UREA ANALOGUES AS HIV-1 PROTEASE INHIBITORS BY USING 3D-QSAR-COMFA METHOD

Rakhi Mishra*, Prem Shankar Mishra, Prof. Shuaib

ABSTRACT

The predicted inhibition constant (Ki) and the predicted inhibitory concentration (IC90) of the HIV-1 protease (HIV-1 PR) inhibitors: – substituted cinnamoyl urea, substituted cinnamoyl phenyl urea derivatives, and cinnamoyl substituted phenyl urea were obtained by the 3D-CoMFA (Comparative Molecular Field Analysis) method. The CoMFA statistical parameters: cross-validate correlation coefficient (q2), higher than 0.5, and the fitted correlation coefficient (r2), higher than 0.90 validated the predicted biological activities. The best predictions were found for the derivative cinnamnoyl phenyl urea with 2-napthyl methyl (log 1/Ki predict = 9.51), 3-(hydroxyl benzyl) (log 1/Ki predict = 9.53) substituents and 2, 3, 4 trifluoro cinnamoyl urea (log 1/Ki predict = 8.33). We attempted to design new potent HIV-1 protease inhibitors by different cinnamoyl urea and cinnamoyl phenyl urea and cinnamoyl substituted phenyl urea derivatives. A favorable steric area surrounding the cinnamoyl analogue, suggest a possible new potent HIV-1 protease inhibitor.

Keywords: 3D-QSAR-CoMFA, the predicted biological activity, substituted cinnamoyl urea, substituted phenyl urea derivatives, HIV-1 protease inhibitors.