Imidazoles have occupied a unique position in heterocyclic chemistry, and its derivatives have attracted considerable interests in recent years for their versatile properties in chemistry and pharmacology. Herein, we report the synthesis of 3-(1-benzyl-2-ethyl-4-nitro-1H-imidazol-5-ylsulfanyl)-1-(4-substituted phenyl-piperazin-1-yl)-propan-1-one 5a-p by reaction of 3-(1-benzyl-2-methyl-4-nitro-1H-imidazol-5-ylsulfanyl)-propanoyl chloride (3) with piperazine nucleophiles. Eighteen compounds were assessed for their antiproliferative inhibition potency against four human cancer cell lines (MCF-7, PC3, MDA MB231 and Du145). Compounds 5f and 5k were the most potent anticancer agents on MCF-7 cell lines cell line with IC50 value of 1.0 µg/mL, while 5d and 5m exhibited cytotoxic effect on PC3 and DU145 cell lines with IC50 values of 4.0 and 5.0 µg/mL, respectively. The molecular docking of compounds 5f, 5d and 5m has been studied.

New piperazine-tagged imidazole derivatives were synthesized via reaction of 1-alkyl/aryl-5-bromo-2-alkyl-4-nitro-1H-imidazoles 1–3 with piperazine nucleophiles. Nine selected compounds were assessed for their antiproliferative inhibition potency against five human cancer cell lines (MCF-7, PC3, Du145, HepG2 and Dermal/Fibroblast). Compounds 7 and 10 are the most potent anticancer agents on HepG2 cell line with IC50 values of (5.6 ± 0.5 µm) and (29.6 ± 7.6 µm) respectively, and on MCF-7 with IC50 values of (32.1 ± 5.6 µm) and (46.2 ± 8.2 µm) respectively. The molecular docking of compounds 7 and 10 has been studied, and the results reveal that the newly designed piperazine-tagged imidazole derivatives bind to the hydrophobic pocket and polar contact with high affinity.

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.

C15H17N3O4S, monoclinic, P21/c (no. 14), a = 8.7938(5) Å, b = 10.3071(4) Å, c = 18.0413(7) Å, β = 79.704(5)°, V = 1608.91(13) Å3, Z = 4, Rgt(F) = 0.0535, wRref(F2) = 0.1447, T = 293(2) K.