engleski

Organometallic iridium complexes as potential anticancer drugs

By using click chemistry approach several new metal complexes with chelating pyridyltriazolylidene ligands were synthesized. Their cytotoxic activity was determined on human cervical carcinoma HeLa cell line by spectrophotometric MTT assay. Compounds ABB43 and SH590 were mostly cytotoxic, with IC50 values of 7.33 μM and 2.01 μM, respectively. Both compounds are organoiridium complexes differing in N1 substituent at the click triazole moiety. Examination of their cytotoxic effect on different cell lines revealed that they preferential kill cancer cells over nontumorigenic cells. Further experiments were performed on HeLa cell line due to their high sensitivity to both investigated complexes. ABB43 and SH590 arrested HeLa cells in S/G2 phase of cell cycle and they induced apoptosis as explored through measurement of Annexin V and propidium iodide binding and measurement of their fluorescence by flow cytometer. To shed more light on the mechanisms responsible for the cytotoxic effect of ABB43 and SH590, we pre-treated HeLa cells with buthionine sulfoximine (inhibitor of glutathione synthesis) and found decreased cell survival upon treatment of cells with either of investigated complexes alone. The pre-treatment of cells with N-acetyl-cysteine (precursor in glutathione synthesis) resulted with opposite effect indicating the possible role of glutathione in protection of cells against ABB43 and SH590 cytotoxicity. We speculate that iridium complexes induce reactive oxidative species in treated cells, which further trigger cell death. Based on the gained knowledge, the development of more tumor-specific anticancer metal complexes as potential anticancer drugs is expected.

anticancer therapy ; organometallic ; complexes ; irridium

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