In Vitro and In Vivo Biological Activities of Dipicolinate Oxovanadium(IV) Complexes

Choroba, Katarzyna; Filipe, Beatriz; Świtlicka, Anna; Penkala, Mateusz; Machura, Barbara; Bieńko, Alina; Cordeiro, Sandra; Baptista, Pedro V.; Fernandes, Alexandra R.

http://hdl.handle.net/10362/160196

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Autores

Fernandes, Alexandra R.

Resumo(s)

The work is focused on anticancer properties of dipicolinate (dipic)-based vanadium(IV) complexes [VO(dipic)(N∩N)] bearing different diimines (2-(1H-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 (5), 4,7-diphenyl-phen (6), and 1,10-phenanthroline (8) 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 in vivo anti-angiogenic capability, and (vi) do not show in vivo toxicity in a chicken embryo.

Descrição

funds granted under the Research Excellence Initiative of the University of Silesia in Katowice. The authors thank Dr inż. Mariola Siwy for measurements of elemental analysis. Publisher Copyright: © 2023 The Authors. Published by American Chemical Society.