Synthesis, Characterization, and Bioactivity of Novel Bicinnolines Having 1-Piperazinyl Moieties

A number of novel bicinnolines containing piperazine moieties, 4a-o, were synthesized via polyphosphoric acid-catalyzed intramolecular cyclization of the respective acyl amidrazone derivatives (3a-o). On the other hand, the amidrazones (3a-o) were prepared by reaction of N ',N ''-(biphenyl-4,4 '-diyl)bis(2-oxopropane hydrazonoyl chloride) (2) with the appropriate cyclic sec-amines in the presence of trimethylamine in absolute ethanol. Structures of the newly synthesized compounds were confirmed by NMR and mass spectral data. The antitumor activity of compounds 4a-o was evaluated in vitro on human breast cancer MDA-231 by a cell viability assay. Results revealed that compounds 4k, 4n, and 4o exhibit potential cytotoxic effects (>70%) on the cancer cells. Additionally, the antimicrobial activity of compounds 4a-o was evaluated against three clinical microbial strains: Escherichia coli (Gram-negative bacteria), Staphylococcus aureus (Gram-positive bacteria), and Candida albicans (fungi/yeast). Results revealed that compounds 4e and 4k exhibit good activity against all three strains included in the study and that compound 4d displays excellent activity against S. aureus strain with a minimum inhibitory concentration value of 0.187 mg/mL.