Probing the anticancer activities of facial trioxorhenium and tricarbonylrhenium compounds with heterocyclic ligands.

Abstract

The cytotoxicity of four rhenium compounds: fac-[ReO₃(impy)CH₃] (1) (impy = 2-(1H-imidazol-2-yl)pyridine), fac-[Re(CO)₃(bzimpy)Cl] (2) (bzimpy = 2-(2-pyridyl)benzimidazole), fac-[Re(CO)₃(bibzimpy)Cl] (3) (bibzimpy = 2,6-bis(2-benzimidazolyl)pyridine) and fac-[Re(CO)₃(impy)Cl] (4) was assessed against cancer cell lines, namely, the cervical hormone-responsive HeLa and the triple-negative breast cancer (TNBC) HCC70 lines versus a non-tumorigenic control breast epithelial cell line, MCF12A. A rare facial trioxorhenium(VII) compound 1 was characterized via various physicochemical techniques. The rhenium compounds 1 - 4 were, in general, more cytotoxic to HeLa cells, compared to the TNBC HCC70 line, displaying half maximal inhibitory concentration (IC₅₀) values in the micromolar range, however, the compounds were not convincingly selective for cancer cells over non-cancerous cells. In particular, compound 4 was highly cytotoxic towards HCC70, HeLa, and MCF12A cells, displaying low micromolar toxicity with IC₅₀ values of 6.57 ± 1.11 μM, 8.88 ± 1.07 and 9.41 ± 1.04 μM in these three cell lines, respectively and was selected for further study as it displayed the greatest cytotoxicity against the highly treatment-resistant HCC70 TNBC cell line. Compound 4 was able to both bind to genomic DNA and act as an intercalator of CT-DNA, however, this did not lead to DNA damage as assessed by a comet assay. In addition, Compound 4 displayed a long-term dose-dependent effect on colony formation and long-term survival as a proxy of in vivo toxicity.