Novel Re(I) Complexes as Potential Selective Theranostic Agents in Cancer Cells and <i>In Vivo</i> in <i>Caenorhabditis elegans</i> Tumoral Strains

Abstract

A series of rhenium(I) complexes of the type <i>fac</i>-[Re(CO)₃(N^N)L]^0/+, <b>Re1</b>-<b>Re9</b>, was synthesized, where N^N = benzimidazole-derived bidentate ligand with an ester functionality and L = chloride or pyridine-type ligand. The new compounds demonstrated potent activity toward ovarian A2780 cancer cells. The most active complexes, <b>Re7</b>-<b>Re9</b>, incorporating 4-NMe₂py, exhibited remarkable activity in 3D HeLa spheroids. The emission in the red region of <b>Re9</b>, which contains an electron-deficient benzothiazole moiety, allowed its operability as a bioimaging tool for <i>in vitro</i> and <i>in vivo</i> visualization. <b>Re9</b> effectivity was tested in two different <i>C. elegans</i> tumoral strains, JK1466 and MT2124, to broaden the oncogenic pathways studied. The results showed that <b>Re9</b> was able to reduce the tumor growth in both strains by increasing the ROS production inside the cells. Moreover, the selectivity of the compound toward cancerous cells was remarkable as it did not affect neither the development nor the progeny of the nematodes.