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KMID : 0043320110340020181
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Archives of Pharmacal Research
2011 Volume.34 No. 2 p.181 ~ p.189
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Synthesis and preliminary evaluation of selected 2-aryl-5(6)-nitro- 1H-benzimidazole derivatives as potential anticancer agents
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Romero-Castro Aurelio
Leon-Rivera Ismael
Avila-Rojas Laura Citlalli
Navarrete-Vazquez Gabriel
Nieto-Rodriguez Alejandro
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Abstract
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In this study we report the synthesis and preliminary evaluation of a series of six 2-aryl-5(6)-nitro-1H-benzimidazole derivatives (1?6) as potential anticancer agents. Cytotoxicity was evaluated against seven human neoplastic cell lines using the MTT assay. Compound 6 [2-(4-chloro-3-nitrophenyl)-5(6)-nitro-1H-benzimidazole] was the most active of the series, showing an IC50 of 28 nM against the A549 cell line. This compound displayed a selective in vitro cytotoxic activity index (>700) in non neoplastic HACAT cells (IC50 = 22.2 μM). Compounds 3 and 6 induce arrest in the S phase of the cell cycle, and compounds 1?6 induce apoptosis in the K562 cell line. Compound 6 induces poly (ADP-ribose) polymerase (PARP) inhibition activity as a potential mechanism of action. These results suggest that compound 6 could be a potent anticancer agent. Compound 3 displayed the best inhibitory activity against PARP with an IC50 value of 0.05 μM, compared to the activity shown by the positive control 3-aminobenzamide (IC50 = 28.5 μM).
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KEYWORD
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Anticancer, Benzimidazole, Nitrocompounds, Cytotoxicity, PARP
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