Oxazoline/amide derivatives against M. tuberculosis: experimental, biological and computational investigations

Abstract

Tuberculosis (TB) is a treatable contagious disease that continuously kills approximately 2 million people yearly. Different oxazoline/amide derivatives were synthesized, and their anti-tuberculosis activity was performed against different strains of Mtb. This study designed the anti-Mtb compounds based on amide and oxazoline, two different structural moieties. The compounds were further synthesized and characterized by spectral techniques. Their anti-Tb activity was evaluated against strain (M. tuberculosis: H37Rv). Selectivity and binding affinity of all synthesized compounds (2a–2e, 3a–3e) against PanK in Mtb were investigated through molecular docking. Molecular dynamics simulation studies for the promising compounds 2d and 3e were performed for 100 ns. The stability of these complexes was assessed by calculating the root mean square deviation, solvent-accessible surface area, and gyration radius relative to their parent structures. Additionally, free energy of binding calculations were performed. Among all synthesized compounds, 2d and 3e had comparable antitubercular activity against standard drug, validated by their computational and biological study.

Keywords:

• M. tuberculosis
• H37Rv
• oxazoline
• amide
• molecular docking
• and simulations

Acknowledgements

The authors are thankful to DST-FIST, Central University of Punjab, Bathinda, for providing the necessary facilities to execute this manuscript.

Disclosure Statement

The authors declare no competing interest

Authors’ contributions

Conceptualization: Prateek Pathak, Om Prakash Verma; Synthesis, biology and computational studies and writing the manuscript: Priyanka Bajpai, Ankit Kumar Singh, Shivanada Kandagalla, Phool Chandra, Vimlendu Kumar Sah; Sketching of figures and data interpretation: Priyanka Bajpai, Ankit Kumar Singh, Shivanada Kandagalla; Writing, review and final editing of the manuscript: Pradeep Kumar, Maria Grishina and Prateek Pathak.

Code availability

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