Avinash Patil, Harleen Duggal, Kamini T Bagul, Sonali Kamble, Pradeep Lokhande, Rajesh Gacche and Rohan Meshram* Pages 1 - 17 ( 17 )
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.
Deoxycytidine triphosphate (dCTP) deaminase, pharmacophore probing, ammonium chloride, 3- arylaminophthalides, 3-indolyl-phthalides, Docking, MMGBSA, target identification.
Department of Chemistry, Savitribai Phule Pune University, Pune, Bioinformatics Centre, Savitribai Phule Pune University, Pune, Bioinformatics Centre, Savitribai Phule Pune University, Pune, Gramin Science (Vocational) College, Vishnupuri, Nanded, Department of Chemistry, Savitribai Phule Pune University, Pune, Department of Biotechnology, Savitribai Phule Pune University, Pune, Bioinformatics Centre, Savitribai Phule Pune University, Pune