Design Design, Synthesis and Evaluation of Antitubercular activity of 4-oxo-butanamido benzoate derivatives

 In light of the inevitable emergence of resistance, designing small molecule-based new drug candidates through structure modulation of the reported drugs has garnered considerable attention. In present study, we have synthesised and characterized 4-oxo-butanamido benzoate derivatives as anti-TB agents through molecular hybridization. A total of 15 target compounds were synthesized. Among all the tested compounds, three compounds (SA1a, SA1b and SA2a) were shown potent anti-TB activity with an MIC = 1.56 µg/ml against M. tuberculosis H37Rv. Further evaluation included the testing for antibacterial and antifungal activities to assess selectivity, revealed neither antibacteial activity nor antifungal activity. Docking studies were conducted to assess binding interactions of the synthesised compounds with the five key enzymes involved in the mycolic acid biosynthesis. Docking results revealed InhA as the potential enzyme target for these compounds. In present study, compounds SA1a, SA1b and SA2a showed highest binding affinity of below -10.0 KCal/mol. The overall conclusion highlighted the activity potency followed para- ≥ meta- > ortho- derivatives, with para derivatives exhibited higher activity even in docking studies.