Synthesis and antimicrobial evaluation of a new hybrid bis-cyanoacrylamide-based-piperazine containing sulphamethoxazole moiety against rheumatoid arthritis-associated pathogens.

Piperazine-based compounds have garnered significant attention due to their notable biological and pharmacological activities, making them essential in fine chemical and pharmaceutical applications. In this study, we managed to synthesize a novel hybrid bis-cyanoacrylamide bearing the piperazine core via phenoxymethyl linker and incorporating sulphamethoxazole moiety. The novel compound was fully characterized using different spectral data including 1H-NMR, C-NMR, and FTIR spectroscopy. Piperazine-based compounds were screened for in silico studies to understand the antimicrobial activity against infections that may contribute to rheumatoid arthritis symptoms. The tested piperazine compound was also evaluated for its antimicrobial activity against Aspergillus niger, Candida albicans, Enterococcus faecalis ATCC 29212, Staphylococcus aureus ATCC 29213, Pseudomonas aeuroginosa ATCC 27853, Escherichia coli ATCC 25922, and Klebsiella pneumoniae ATCC 700603. S. aureus showed the highest inhibition, with a zone diameter of 16.0 ± 1.0 mm at a concentration of 0.8 mg/ml. The minimal inhibitory concentration (MIC) for all bacterial species ranged from 5 to 40 mg/ml. In contrast, fungal species were the most resistant to the tested compound. Molecular docking studies were conducted to elucidate the interaction mechanisms, binding energies, and hydrogen bonding interactions within protein-ligand complexes. Molecular docking studies were performed against five bacterial proteins and two fungal proteins, including DNA gyrase subunit B (UniProt ID: Q839Z1), protein RecA of (UniProt ID: P0A7G6), cyclic AMP-AMP-AMP synthase (UniProt ID: P0DTF7), UDP-N-acetylglucosamine 1-carboxyvinyl transferase (UniProt ID: A0A1S5RKE3), and clumping factor A (UniProt ID: Q53653). The tested compound achieved the highest binding score of ∆G =  - 10.9 kcal/mol at the cyclic AMP synthase active site (UniProt ID: P0DTF7), forming 26 interactions. The results demonstrated that the synthesized piperazine compound exhibits promising antibacterial and antifungal activities, highlighting its potential as a candidate for antimicrobial development.