Some characteristics of activity of potential chemotherapeutics--benzimidazole derivatives.
In this work, the biological activity of some benzimidazoles and benzimidazole-4,7-diones was compared. These two groups of compounds were evaluated as potential chemotherapeutics and their characteristic relationship structure to biological activity was discussed. The authors compared their effect into the cytotoxic, apoptosis and DNA destruction approach. Their cytotoxic effect on the human lung adenocarcinoma A549 cells line was determined by WST-1 test. Next the cytotoxic way of tumor cells death was determined by caspase 3/7 test. The last point referred to the DNA destruction of A549 cells and test in situ DNA Assay Kit was applied. Two of the examined compounds (B2 and D2) show a very good correlation of the cytotoxic effect normoxia to hypoxia and they have been found as the potential agents of the DNA damage. The most cytotoxic feature possesses N-oxide benzimidazole derivatives (D and B groups). The screening test of the DNA damage established that N-oxide benzimidazole derivatives (D and B groups) can be more potent as the hypoxia-selective agents for tumor cells than benzimidazole derivatives (A and C groups). Additionally, the test of the caspase-dependent apoptosis proved that the exposure of benzimidazole-4,7-diones against A549 cells, especially in hypoxia, promotes apoptotic cell death.
Department of Pharmaceutical Chemistry, Drug Analysis and Radiopharmacy, Medical University of Lodz, Lodz, Poland. Electronic address: katarzyna.blaszczak-swiatkiewicz@umed.lodz.pl.
Katarzyna
K
Błaszczak-Świątkiewicz
Department of Pharmaceutical Chemistry, Drug Analysis and Radiopharmacy, Medical University of Lodz, Lodz, Poland.
Elżbieta
E
Mikiciuk-Olasik
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis; D001562:Benzimidazoles / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D006801:Humans
D000970:Antineoplastic Agents; D001562:Benzimidazoles; C031000:benzimidazole
Anticancer activity; Benzmidazole-4,7-dione; Bioreductive agents; Bioreductive prodrugs; Hypoxia