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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. January 2010, Volume 9, Number 1, 1-19 |
Predictive Comparative QSAR Modeling of 4-Pyridones as Potent Antimalarials
Nilanjan Adhikari, Milan Kumar Maiti, and Tarun Jha
Internet Electron. J. Mol. Des. 2010, 9, 1-19
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Abstract:
Malaria is one of the most life threatening diseases in tropical developing world.
Chloroquine resistance occurs due to mutation in protozoal genes. It has got significance
to synthesize new drugs for targeting specific enzyme or bind with receptor or to disrupt
the life cycle of P. falciparum. Principal component regression analysis (PCRA),
stepwise regression, factor analysis multiple linear regression (FA-MLR), partial least
squares (PLS) and factor analysis partial least squares (FA-PLS) techniques were applied
on some 4-pyridones to find structurally significant quantitative structure-activity
relationship (QSAR) models developed using different descriptors for further improved
antimalarial activity. Comparative QSAR study was performed on some 4-pyridones by
using PCRA, stepwise regression, FA-MLR, PLS and FA-PLS techniques to find
structural requirements for further improved antimalarial activity. The QSAR study
shows significances of electrotopological state atom index (ETSA) indices as well as
frontier electron density at atom numbers 1 and 9, grid surface area and molecular
volume. These may be beneficial for the potent antimalarial activity. It also reveals that at
atom numbers 1 and 9 electrophilic attack may be favorable for higher antimalarial
activity. Electrostatic potential at the atom number 1 may also play pivotal role in the
antimalarial activity of 4-pyridones. Electrophilic substitution as well as electronic
interactions at atom 1 and 9 and increasing molecular volume and grid surface area of
4-pyridones may be beneficial for higher antimalarial activity.
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