Green synthesis, antitubercular evaluation, and molecular docking studies of ethyl 3,5-dicyano-6-oxo-2,4-diarylpiperidine-3-carboxylate derivatives

Abstract

A simple and environment friendly one-pot synthesis of ethyl 3,5-dicyano-6-oxo-2,4-diarylpiperidine-3-carboxylate derivatives from aryl aldehydes, ethyl cyanoacetate, and ammonium acetate was developed in aqueous medium without using a catalyst. The significant features of this method are easy, inexpensive experimental procedures with short reaction time and high yield. The use of water as the solvent without catalyst makes the reaction meritorious and further fulfilled green chemistry protocols. The compounds were screened for antibacterial activity against Gram-positive bacteria (Staphylococcus aureus 25923) and Gram-negative bacteria (Escherichia coli ATCC25922) by disk diffusion method. Compounds 4f, 4h, and 4i showed moderate antibacterial activity S. aureus. Intriguingly, compound 4g exhibited very good antibacterial activity against E. coli. Antitubercular activity assay indicates that the compounds 4(a–c) exhibited activity with varying MICs against mycobacterium tuberculosis H37RV control strain and multidrug-resistant tuberculosis (MDR-TB) clinical isolate. Among the three tested compounds, 4c showed an equipotent antitubercular activity against H37Rv and MDR-TB clinical isolates with MIC 3.13 μg/ml. Further, docking analysis of synthesized piperidinone derivatives with acetate kinase protein reported that these compounds interact effectively with the catalytic residues that are in the vicinity of ATP binding and active sites facilitating inhibition of enzyme function. Thus these derivatives can be promising compounds for antitubercular activity to combat tuberculosis.