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

Chem Biol Interact. 2024 Dec 15:406:111351. doi: 10.1016/j.cbi.2024.111351. Online ahead of print.

Abstract

The cytotoxicity of four rhenium compounds: fac-[ReO3(impy)CH3] (1) (impy = 2-(1H-imidazole-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.

Keywords: Anti-Cancer studies; Crystal structure; DNA binding; Heterocyclic; Rhenium; Spectroscopic data.