title: Novel Zinc(II) Complexes [Zn(atc-Et)₂] and [Zn(atc-Ph)₂]: In Vitro and in Vivo Antiproliferative Studies.
abstract: 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.
authors.affiliation: Faculdade de Ciencias Farmaceuticas, UNESP-Univ Estadual Paulista, Campus Araraquara, Araraquara, São Paulo 14800-903, Brazil. ericaoliveir@bol.com.br.
authors.forename: Erica de O
authors.initials: Ede O
authors.lastname: Lopes
authors.affiliation: Instituto de Química de São Carlos, USP-Univ de São Paulo, São Carlos, São Paulo 13560-970, Brazil. carolsatrini@gmail.com.
authors.forename: Carolina G de
authors.initials: CG
authors.lastname: Oliveira
authors.affiliation: Faculdade de Ciencias Farmaceuticas, UNESP-Univ Estadual Paulista, Campus Araraquara, Araraquara, São Paulo 14800-903, Brazil. patrbent@yahoo.com.br.
authors.forename: Patricia B da
authors.initials: PB
authors.lastname: Silva
authors.affiliation: Centro de Estudos Ambientais, UNESP-Univ Estadual Paulista, Campus Rio Claro, Rio Claro, São Paulo 13506-900, Brazil. kadueismann@gmail.com.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Eismann
authors.affiliation: Centro de Estudos Ambientais, UNESP-Univ Estadual Paulista, Campus Rio Claro, Rio Claro, São Paulo 13506-900, Brazil. suarezcarlos@yahoo.com.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Suárez
authors.affiliation: Centro de Estudos Ambientais, UNESP-Univ Estadual Paulista, Campus Rio Claro, Rio Claro, São Paulo 13506-900, Brazil. amenega@rc.unesp.br.
authors.forename: Amauri A
authors.initials: AA
authors.lastname: Menegário
authors.affiliation: Faculdade de Ciencias Farmaceuticas, UNESP-Univ Estadual Paulista, Campus Araraquara, Araraquara, São Paulo 14800-903, Brazil. claricequeico@gmail.com.
authors.forename: Clarice Q F
authors.initials: CQ
authors.lastname: Leite
authors.affiliation: Instituto de Química de São Carlos, USP-Univ de São Paulo, São Carlos, São Paulo 13560-970, Brazil. deflon@iqsc.usp.br.
authors.forename: Victor M
authors.initials: VM
authors.lastname: Deflon
authors.affiliation: Faculdade de Ciencias Farmaceuticas, UNESP-Univ Estadual Paulista, Campus Araraquara, Araraquara, São Paulo 14800-903, Brazil. fernandopavan@fcfar.unesp.br.
authors.forename: Fernando R
authors.initials: FR
authors.lastname: Pavan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D001156:Artemia; D001682:Biological Availability; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D015394:Molecular Structure; D013882:Thiosemicarbazones / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D023382:Toxicity Tests, Acute; D015032:Zinc / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D013882:Thiosemicarbazones; D015032:Zinc
keywords: Artemia salina L.; acute toxicity; antiproliferative activity; cancer; oral bioavailability; zinc(II) complexes