Amide-Linked Monocarbonyl Curcumin Analogues: Efficient Synthesis, Antitubercular Activity and Molecular Docking Study

Abstract

An approach toward the synthesis of novel conjugates of 3,5-bis (arylidene)-4-piperidones (DAP) pharmacophore with amide-linkage has been developed via one-pot multicomponent reaction of aryl aldehydes, piperidinone and 2-chloro-N-phenylacetamide using [Et₃NH][HSO₄] as a catalyst/medium. Both substitutions on arylidene rings and piperidinone nitrogen (substituted 2-chloro-N-phenylacetamide) were varied. The synthesized conjugates were evaluated for their in vitro antitubercular activity against M. tuberculosis H₃₇Ra (MTB) and M. bovis BCG strains. Among the series, compounds 4f, 4g, 4i and 4j showed remarkable broad spectrum antitubercular activity with low IC₅₀ values. Furthermore, computer docking simulations, for the most active conjugates were performed with the active site of mycobacterial enoyl-acyl carrier protein reductase (InhA) support the antitubercular activity. Lower cytotoxicity, high potency and promising activity against MTB and M. Bovis BCG suggest that amide linked DAP could serve as good leads for further modifications and development.

Graphical Abstract

Keywords:

• Bis (arylidene)-4-piperidones
• Ionic liquid
• Antimycobacterial activity
• Cytotoxicity
• Molecular docking Study

Acknowledgments

DDS and MHS are very much grateful to the Council of Scientific and Industrial Research (CSIR), New Delhi, India for the award of research fellowship. Authors are also thankful to the Head, Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University, for providing laboratory facility and University Grants Commission, Department of Science and Technology, New Delhi for financial support under DST-FIST and UGC-SAP Schemes.

Disclosure statement

There are no conflicts of interest.