Abstract
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 IC(50) of 28 nM against the A549 cell line. This compound displayed a selective in vitro cytotoxic activity index (>700) in non neoplastic HACAT cells (IC(50) = 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 IC(50) value of 0.05 μM, compared to the activity shown by the positive control 3-aminobenzamide (IC(50) = 28.5 μM).
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Antineoplastic Agents / chemical synthesis*
-
Antineoplastic Agents / chemistry
-
Antineoplastic Agents / pharmacology*
-
Apoptosis / drug effects*
-
Benzamides / pharmacology
-
Benzimidazoles / chemical synthesis*
-
Benzimidazoles / chemistry
-
Benzimidazoles / pharmacology*
-
Cell Cycle / drug effects*
-
Cell Line
-
Cell Line, Tumor
-
Drug Screening Assays, Antitumor
-
Enzyme Inhibitors / chemistry
-
Enzyme Inhibitors / pharmacology
-
Humans
-
Molecular Structure
-
Molecular Targeted Therapy
-
Nitro Compounds / chemical synthesis
-
Nitro Compounds / chemistry
-
Nitro Compounds / pharmacology
-
Nitrobenzenes / chemical synthesis
-
Nitrobenzenes / chemistry
-
Nitrobenzenes / pharmacology
-
Poly(ADP-ribose) Polymerase Inhibitors*
-
Poly(ADP-ribose) Polymerases / metabolism
Substances
-
2-(4-chloro-3-nitrophenyl)-5(6)-nitro-1H-benzimidazole
-
Antineoplastic Agents
-
Benzamides
-
Benzimidazoles
-
Enzyme Inhibitors
-
Nitro Compounds
-
Nitrobenzenes
-
Poly(ADP-ribose) Polymerase Inhibitors
-
3-aminobenzamide
-
Poly(ADP-ribose) Polymerases