Novel Zinc(II) Complexes [Zn(atc-Et)₂] and [Zn(atc-Ph)₂]: In Vitro and in Vivo Antiproliferative Studies.
Cisplatin and its derivatives are the main metallodrugs used in cancer therapy. However, low selectivity, toxicity and drug resistance are associated with their use. The zinc(II) (Zn(II)) thiosemicarbazone complexes [Zn(atc-Et)₂] (1) and [Zn(atc-Ph)₂] (2) (atc-R: monovalent anion of 2-acetylpyridine N4-R-thiosemicarbazone) were synthesized and fully characterized in the solid state and in solution via elemental analysis, Fourier transform infrared (FTIR), ultraviolet-visible (UV-Vis) and proton nuclear magnetic resonance (¹H NMR) spectroscopy, conductometry and single-crystal X-ray diffraction. The cytotoxicity of these complexes was evaluated in the HepG2, HeLa, MDA-MB-231, K-562, DU 145 and MRC-5 cancer cell lines. The strongest antiproliferative results were observed in MDA-MB-231 and HepG2 cells, in which these complexes displayed significant selective toxicity (3.1 and 3.6, respectively) compared with their effects on normal MRC-5 cells. In vivo studies were performed using an alternative model (Artemia salina L.) to assure the safety of these complexes, and the results were confirmed using a conventional model (BALB/c mice). Finally, tests of oral bioavailability showed maximum plasma concentrations of 3029.50 µg/L and 1191.95 µg/L for complexes 1 and 2, respectively. According to all obtained results, both compounds could be considered as prospective antiproliferative agents that warrant further research.
['Lopes|Erica de O|Ede O|', 'Oliveira|Carolina G de|CG|', 'Silva|Patricia B da|PB|', 'Eismann|Carlos E|CE|', 'Suárez|Carlos A|CA|', 'Menegário|Amauri A|AA|', 'Leite|Clarice Q F|CQ|', 'Deflon|Victor M|VM|', 'Pavan|Fernando R|FR|']
D000818:Animals D000970:Antineoplastic Agents D001156:Artemia D001682:Biological Availability D045744:Cell Line, Tumor D049109:Cell Proliferation D006367:HeLa Cells D056945:Hep G2 Cells D006801:Humans D066298:In Vitro Techniques D051379:Mice D015394:Molecular Structure D013882:Thiosemicarbazones D023382:Toxicity Tests, Acute D015032:Zinc
zinc(II) complexes cancer Artemia salina L. oral bioavailability acute toxicity antiproliferative activity