<i>In Vitro</i> and <i>In Vivo</i> Biological Activities of Dipicolinate Oxovanadium(IV) Complexes

Abstract

The work is focused on anticancer properties of dipicolinate (dipic)-based vanadium(IV) complexes [VO(dipic)(N^∩N)] bearing different diimines (2-(1<i>H</i>-imidazol-2-yl)pyridine, 2-(2-pyridyl)benzimidazole, 1,10-phenanthroline-5,6-dione, 1,10-phenanthroline, and 2,2'-bipyridine), as well as differently 4,7-substituted 1,10-phenanthrolines. The antiproliferative effect of V(IV) systems was analyzed in different tumors (A2780, HCT116, and HCT116-DoxR) and normal (primary human dermal fibroblasts) cell lines, revealing a high cytotoxic effect of [VO(dipic)(N^∩N)] with 4,7-dimethoxy-phen (<b>5</b>), 4,7-diphenyl-phen (<b>6</b>), and 1,10-phenanthroline (<b>8</b>) against HCT116-DoxR cells. The cytotoxicity differences between these complexes can be correlated with their different internalization by HCT116-DoxR cells. Worthy of note, these three complexes were found to (i) induce cell death through apoptosis and autophagy pathways, namely, through ROS production; (ii) not to be cytostatic; (iii) to interact with the BSA protein; (iv) do not promote tumor cell migration or a pro-angiogenic capability; (v) show a slight <i>in vivo</i> anti-angiogenic capability, and (vi) do not show <i>in vivo</i> toxicity in a chicken embryo.