Objective: The study aims at the derivatization of “Phthalides” and synthesizes 3-
arylaminophthalides & 3-indolyl-phthalides compounds, and evaluates their anti-tubercular and
antioxidant activities. The study has also intended to employ the in silico methods for the
identification of possible drug targets in Mycobacterium and evaluate the binding affinities of
Methods: This report briefly explains the synthesis of phthalide derivatives using ammonium
chloride. The synthesized compounds were characterized using spectral analysis. Resazurin Microtiter
Assay (REMA) plate method was used to demonstrate the anti-mycobacterial activity of the
synthesized compounds. An in-silico pharmacophore probing approach was used for target
identification in Mycobacterium. The structural level interaction between the identified putative drug
target and synthesized phthalides was studied using Lamarckian genetic algorithm-based software.
Results and Discussion: In the present study, we report an effective, environmentally benign
scheme for the synthesis of phthalide derivatives. Compounds 5c and 5d from the current series
appear to possess good anti-mycobacterial activity. dCTP: deaminasedUTPase was identified as a
putative drug target in Mycobacterium. The docking results clearly showed the interactive
involvement of conserved residues of dCTP with the synthesized phthalide compounds.
Conclusion: On the eve of evolving anti-TB drug resistance, the data on anti-tubercular and allied
activities of the compounds in the present study demonstrates the enormous significance of these
newly synthesized derivatives as possible candidate leads in the development of novel anti-tubercular
agents. The docking results from the current report provide a structural rationale for the promising
anti-tubercular activity demonstrated by 3-arylaminophthalides and 3-indolyl-phthalides compounds.