The development of new HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs) offers the possibility of generating structures of increased potency. To this end, a series of 1-(1-benzyl-2-ethyl-4-nitro-1H-imidazol-5-yl)-4-(1,1 -biaryl)-4-yl-piperazine derivatives (6a-l) was synthesized via the Suzuki coupling reaction. Analogously, coupling of the acid derivative 5, prepared from 4, with various amino acid methyl esters in the presence of HOBt/DCC reagents afforded the benzamide derivatives 8-11. The newly synthesized compounds were assayed against HIV-1 and HIV-2 in MT-4 cells. All compounds are inactive, except compound 6f which showed inhibition of HIV-1 with EC 50 = 2.60 µg mL −1 with a selectivity index (SI) of 9.
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.
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