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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. November 2007, Volume 6, Number 11, 363-374 |
QSAR Prediction of HIV-1 Reverse Transcriptase Inhibitory Activity of Benzoxazinone Derivatives
Veerasamy Ravichandran, Vishnu Kant Mourya, and Ram Kishore Agrawal
Internet Electron. J. Mol. Des. 2007, 6, 363-374
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Abstract:
Inhibition of HIV-1 reverse transcriptase (RT) is an important strategy for
the treatment of HIV and AIDS. Therefore, HIV-1 RT inhibitory activity
of benzoxazinone derivatives has been analyzed with different
physicochemical parameters. In the present work, quantitative
structure- activity relationship (QSAR) studies were performed on a series of
benzoxazinones as HIV-1 reverse transcriptase inhibitors using the
modeling software WinCAChe version 6.1 and Chem Draw Ultra version 8.
The multiple linear regression analysis was performed to derive
quantitative structure-activity relationship models that were further
evaluated for statistical significance and predictive power by internal and
external validation. The best QSAR model was selected having a
correlation coefficient (r) of 0.833, r2 of 0.694 with standard error of
estimation (SEE) 0.278 and cross-validated squared correlation coefficient
(r2cv) of 0.615. The robustness of the model was checked by Y-randomization
test and it was found to be a good predictive model. The
model suggest that increase in electron withdrawing groups leads to loss
of fit of molecules with the enzyme binding site, which decreases the
HIV-1 RT binding affinities. The positive coefficient of INH showed that
the replacement of the 3rd position carbon atom of benzoxazinone with NH
is an important determinant for the inhibitory activity. The positive
coefficient of ICP indicats that the cyclopropyl group at the R1 position is
most favorable for HIV-1 RT inhibitory activity.
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