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Int. J. Mol. Sci. 2016, 17(5), 781;

Novel Zinc(II) Complexes [Zn(atc-Et)2] and [Zn(atc-Ph)2]: In Vitro and in Vivo Antiproliferative Studies

Faculdade de Ciencias Farmaceuticas, UNESP—Univ Estadual Paulista, Campus Araraquara, Araraquara, São Paulo 14800-903, Brazil
Instituto de Química de São Carlos, USP—Univ de São Paulo, São Carlos, São Paulo 13560-970, Brazil
Centro de Estudos Ambientais, UNESP—Univ Estadual Paulista, Campus Rio Claro, Rio Claro, São Paulo 13506-900, Brazil
Author to whom correspondence should be addressed.
Academic Editor: Sotiris Hadjikakou
Received: 31 March 2016 / Revised: 2 May 2016 / Accepted: 6 May 2016 / Published: 21 May 2016
(This article belongs to the Special Issue Recent Advances in Metal Based Drugs)
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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) (ZnII) 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. View Full-Text
Keywords: zinc(II) complexes; cancer; antiproliferative activity; Artemia salina L.; acute toxicity; oral bioavailability zinc(II) complexes; cancer; antiproliferative activity; Artemia salina L.; acute toxicity; oral bioavailability

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Lopes, E.O.; Oliveira, C.G.; Silva, P.B.; Eismann, C.E.; Suárez, C.A.; Menegário, A.A.; Leite, C.Q.F.; Deflon, V.M.; Pavan, F.R. Novel Zinc(II) Complexes [Zn(atc-Et)2] and [Zn(atc-Ph)2]: In Vitro and in Vivo Antiproliferative Studies. Int. J. Mol. Sci. 2016, 17, 781.

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