Insights into structures of imidazo oxazines as potent polyketide synthase XIII inhibitors using molecular modeling techniques

Abstract

Tuberculosis, a major global health concern, and its drug development toward the disease are too devastating to meet the clinical demands. The present work emphasizes a detailed QSAR study using QSARINS which developed descriptors favoring an excellent model equation. The best model equation generated has four variables namely AlogP, ATSc4, mindssC, and MDEC23 with statistical values R² = 0.7406, LOF = 0.1858, CCC_tr = 0.8510, Q₂LOO = 0.6569, Q₂LMO = 0.6286, CCC_cv = 0.8037, R²_ext = 0.8600, and CCC_ext = 0.9252. The developed QSAR model justifies that the key structural fragments highly correlate with activity. Docking the designed compounds with PKS XIII, a novel target catalyzes the formation of mycolic acids and its results distinctly improve expected antitubercular activity showing all probable interactions. Compounds were further screened for ADME analysis and toxicity.

Keywords: ADMET; PKS13; QSARINS; nitro imidazo oxazines; toxicity.