Investigation of alkylating, antineoplastic and anti-HIV potentials of the chalcones: 2-(3-arylpropenoyl)benzimidazole and their corresponding N1-methyl derivatives.
A series of 2-(3-Arylpropenoyl)benzimidazole, 3a-d, and their corresponding N1-methyl analogues, 3e-h, were synthesized from p-substituted benzaldehyde and 2-acetylbenzimidazole or 2-acetyl-1-methylbenzimidazole, respectively. The in vitro alkylating activities of these alpha-beta-unsaturated ketones were investigated using L-cysteine as a model of cellular thioles at pH 7.4 and 37 degrees C. No significant difference between the alkylating activities of 3a-d and 3e-h as expressed from the pseudo first-order rate constants of the reactions of these derivatives with L-cysteine monitored by HPLC. However, significant variations in the rates of alkylation among these derivatives relative to the p-substituted group on the aryl moiety were observed, which is attributable to the electronic parameters of the substituted groups. The in vitro cytotoxic activity provided that the p-nitro derivative; 3d has some selectivity for cell lines of leukemia, renal cancer and breast cancer. The compounds were completely inactive as anti-HIV agents. Molecular modeling for all derivatives was undertaken.
Aboul-Fadl
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Department of Pharmaceutical Medicinal Chemistry, Assiut University, Assiut 71526, Egypt.
El-Shorbagi
A N
AN
Hozien
Z A
ZA
Sarhan
A W
AW
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis* / Q000494:pharmacology; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D002599:Chalcone / Q000138:chemical synthesis* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008745:Methylation; D008958:Models, Molecular; D014407:Tumor Cells, Cultured
D019380:Anti-HIV Agents; D018906:Antineoplastic Agents, Alkylating; D001562:Benzimidazoles; D002599:Chalcone