Design, synthesis and characterization of ethyl 3‐benzoyl‐7‐morpholinoindolizine‐1‐carboxylate as anti‐tubercular agents: In silico screening for possible target identification

Abstract A thorough search for the development of innovative drugs to treat tuberculosis, especially considering the urgent need to address developing drug resistance, we report here a synthetic series of ethyl 3‐benzoyl‐7‐morpholinoindolizine‐1‐carboxylate analogues ( 5a‐o ) as potent anti‐tubercular agents. These morpholino‐indolizines were synthesized by reacting 4‐morpholino pyridinium salts, with various electron‐deficient acetylenes to afford the ethyl 3‐benzoyl‐7‐morpholinoindolizine‐1‐carboxylate analogues ( 5a‐o ). All synthesized intermediate and final compounds are characterized by spectroscopic methods such as 1 H NMR, 13 C NMR and HRMS and further examined for their anti‐tubercular activity against the M. tuberculosis H37Rv strain (ATCC 27294—American type cell culture). All the compounds screened for anti‐tubercular activity in the range of 6.25–50 μM against the H37Rv strain of Mycobacterium tuberculosis . Compound 5g showed prominent activity with MIC 99 2.55 μg/mL whereas compounds 5d and 5j showed activity with MIC 99 18.91 μg/mL and 25.07 μg/mL, respectively. In silico analysis of these compounds revealed drug‐likeness. Additionally, the molecular target identification for Malate synthase (PDB 5CBB) is attained by computational approach. The compound 5g with a MIC 99 value of 2.55 μg/mL against M. tuberculosis H37Rv emerged as the most promising anti‐TB drug and in silico investigations suggest Malate synthase (5CBB) might be the compound's possible target.