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.

Graphical Abstract

Keywords:

• QSARINS
• PKS13
• nitro imidazo oxazines
• toxicity
• ADMET

Acknowledgments

We thank the Research Council of SRMIST and The Dean, SRM College of Pharmacy for their valuable support. We also express our gratitude to Dr. Paolo Gramatica, for providing QSARINS the academic license software, and who is heading the QSAR Research Unit, Insubria University, Italy.

Disclosure statement

No potential conflict of interest was reported by the author(s).