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

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 (H-1 and C-13) 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 mu m) and against PC3 with IC50 value of (9.00 +/- 0.028 mu m). 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.

Automated summary

Piperazine-tagged imidazole derivatives 3a and 5-11 were synthesized and evaluated for their anticancer activity. Compound 5 showed the highest potency against MCF-7 and PC3 cell lines, binding to the hydrophobic pocket and forming polar contacts with high affinity.