Biological evaluation of the toxicity and the cell cycle interruption by some benzimidazole derivatives

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Abstract

In this work, the in vitro tests of biological activity of benzimidazoles were conducted. This group of benzimidazole derivatives was evaluated as potential bioreductive agents and their characteristic pro-apoptosis activity and cell cycle interruption on the human lung adenocarcinoma A549 cells were discussed. Their toxicity on the healthy human erythrocytes and their influence on the healthy human erythrocytes acetylcholinesterase enzyme (AChE) were established. Their apoptosis activity on A549 cells line was determined by Annexin V-APC test, and it was visualized by Hoechst test. In the next stage, their influence on the cell cycle interruption was determined by using the ribonuclease reagent. The AChE inhibition test was defined by the Ellman method, and the red blood cell lysis was defined by erythrotoxicity test. The results proved the pro-apoptosis properties of all tested compounds in normoxia and hypoxia. The DNA content assay showed that the benzimidazoles possess the ability to interrupt S phase of tumor cell cycle. The best activity in this action was presented by compound 1, especially in hypoxia, and it proves that the N-oxide analogs are predispositioned to the hypoxic target. In this study, the benzimidazoles were found as potentially biocompatible and their inhibition of acetylcholinesterase was lower than tirapazamine and much lower than tacrine which constitutes their desired effect of potential biological activity.

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Błaszczak-Świątkiewicz, K., Sikora, J., Szymański, J., Danilewicz, M., & Mikiciuk-Olasik, E. (2016). Biological evaluation of the toxicity and the cell cycle interruption by some benzimidazole derivatives. Tumor Biology, 37(8), 11135–11145. https://doi.org/10.1007/s13277-016-4828-1

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