Nitroimidazoles Part 10. Synthesis, crystal structure, molecular docking, and anticancer evaluation of 4-nitroimidazole derivatives combined with piperazine moiety

Abstract Piperazine-tagged imidazole derivatives 3a (symmetrical di-substituted piperazine) and 5–11 were synthesized through the combination of 4-nitroimidazole derivatives with piperazine moiety. The structural characterization was done by different physical and spectral techniques like NMR (1H and 13C) and mass spectrometry. The constituency of compound 3a was confirmed by X-ray structural analyses. All compounds were assessed for their antiproliferative inhibition potency against five human cancer cell lines namely MCF-7, PC3, MDA-231, A549 and Fibro dental. Compound 5 was found to be the most potent anticancer agents against MCF-7 cell line with IC50 values of (1.0 ± 0 µm) and against PC3 with IC50 value of (9.00 ± 0.028 µm). The molecular docking of compound 5 had been studied, and the results revealed that the newly designed 4-nitroimidazole combined with piperazine moiety derivatives bond to the hydrophobic pocket and polar contacts with high affinity.