Synthesis of new 3-arylaminophthalides and 3-indolyl-phthalides using ammonium chloride, evaluation of their anti-mycobacterial potential and docking study.

OBJECTIVE: The study aims at derivatization of "Phthalides" to artificially synthesize 3-arylaminophthalides and 3-indolylphthalides compounds. Evaluate the Anti-tubercular and Antioxidant Scavenging activity of the synthesised phthalide derivatives. Followed by, Identification of a target for these compounds and evaluating their binding modes. METHOD: This report briefs the synthesis of phthalide compounds using ammonium chloride. Resazurin microtiter assay (REMA) plate method was used to study the anti-microbial activity of these compounds. In-silico pharmacophore probing approach is used for target identification in Mycobacterium. The interaction at the structural level between the identified putative target and synthesised phthalides were studied using a Lamarckian genetic algorithm-based software. RESULTS: In the present study we report effective, environmentally benign scheme for synthesis of phthalide derivatives. Compound 5c and 5d from current series appear to possess good anti-mycobacterial activity. dCTP: deaminase dUTPase was identified as a putative drug target. The docking results from current report indicate involvement of conserved residues from the enzyme. CONCLUSION: The data on anti-tubercular and allied activities of the compounds in present study demonstrates enormous potential of these newly synthesized derivatives in development of novel anti-tubercular agents. The docking results from current report provide a structural rationale behind observed anti-tubercular activity via 3-arylaminophthalides and 3- indolyl-phthalides compounds.