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Antiproliferative activity of new benzimidazole derivatives

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Błaszczak-Świątkiewicz K., Olszewska P., Mikiciuk-Olasik E.
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2013
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vol. 60
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issue 3
427-433
EN
A series of new benzimidazole derivatives were synthesized and tested in vitro for possible anticancer activity. Their effect of proliferation into selected tumor cell lines at normoxia and hypoxia conditions was determined by WST-1 test. Additionally, apoptosis test (caspase 3/7 assay) was used to check the mode caused by the agents of cell death. Four of the examined compounds (7, 8, 13, 11) showed a very good antiproliferative effect and three of them were specific for hypoxia conditions (8, 14, 11). Compound 8 was the most cytotoxic against human lung adenocarcinoma A549 cells at hypoxic conditions. Hypoxia/ normoxia cytotoxic coefficient of compound 14 (4.75) is close to hypoxia/normoxia cytotoxic coefficient of tirapazamine (5.59) - a reference compound in our experiments and this parameter locates it between mitomycin C and 2-nitroimidazole (misonidazole). Screening test of caspase-dependent apoptosis proved that exposure to A549 cells of compounds 7-8 and 13-14 for 48 h promote apoptotic cell death. These results supplement our earlier study of the activity of new potentialy cytotoxic heterocyclic compounds against selected tumor cells.
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