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

• Published in: Pharmaceutical chemistry journal 2021-12, Vol.55 (9), p.886-907
• Main Authors: Bhuvaneswari, S., Aakash, V. Bala, Ramalakshmi, N., Arunkumar, S.
• Format: Article
• Language: English
• Subjects: Analysis; DNA; Medicine; Organic Chemistry; Pharmacology/Toxicology; Pharmacy
• ISSN: 0091-150X; 1573-9031
• DOI: 10.1007/s11094-021-02513-x

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.