Quantitative Structure-Activity Relationship Analysis and Validation of New DNA Gyrase Inhibitors

Quantitative structure-activity relationship (QSAR) analysis was carried out for a series of 61 compounds with thiazole and benzthiazole moiety for inhibition of the DNA gyrase enzyme of Escherichia coli. The study was performed by conducting multiple linear regression analysis and followed by validation of the models by OCED principles. Four models were selected as the best with r(2) values greater than 0.7. Validation was performed by the leave-one-out method to ensure stability. The predictive power was examined by the Golbraikh and Tropsha conditions. Reliability of the models was checked by constructing Williams plots. The Y-randomization and prediction error based validation were also performed. All the four selected models had r(2) values greater than 0.74 and Q(2) values greater than or equal to 0.66. All models obeyed the Golbraikh and Tropsha conditions. The compounds were found to lie within the warning leverage in the Williams plot. The Y-randomization also resulted in values above 0.6, and model 1 was found to be good in prediction error based validation. Compounds with thiazole and benzthiazole moiety proved to inhibit DNA gyrase enzyme as a lead molecule. Lead optimization can be performed by designing new compounds based on the obtained QSAR results.