Title: 3D QSAR study of Fluoroquinolone Derivatives as DNA Gyrase Inhibitors
Author: Kavan. M. Jani
DOI: https://dx.doi.org/10.18535/jmscr/v6i6.112
Abstract
Tuberculosis is one of the major challenges around globe caused by Mycobacterium Tuberculosis. As per WHO, the rate of disease increases by 0.4% per year. DNA Gyrase being a potent target, a promising tool for the treatment of tuberculosis. Amongst all the moeity used for study, fluroquinolone plays a key role in drug discovery and development. In order to know the structural requirements of the respective target, three-dimensional quantitative structure activity relationship (3D-QSAR) was performed on fluoroquinolone series. CoMFA and CoMSIA techniques were used to examine the structural requirements of DNA Gyrase inhibitors. The developed models indicates the high cross-validation co-efficient (q2) of 0.644 and 0.646 and non-cross validated co-efficient (r2) of 0.985 and 0.983 respectively. The validation of predictive ability of the models were carried out using external validation of predictive factor (r2pred) of 0.685and 0.732 respectively. These signify that the model possess high statistical reliability and good predictive power. The 3D contour maps were generated from CoMFA and CoMSIA models. Based on the, contour maps generated, the important structural features of DNA Gyrase inhibitors, with potentially higher predicted activity can be helpful for designing of new molecules. Consequently, the results obtained may provide important information in further augmentation of fluoroquinolone derivatives as DNA Gyrase inhibitors.
Keywords: DNA Gyrase, CoMFA, CoMSIA, Fluoroquinolone.
