Preparation, cytotoxic activity and DNA interaction studies of new platinum(II) complexes with 1,10-phenanthroline and 5-alkyl-1,3,4-oxadiazol-2(3H)-thione derivatives.

Autor: Souza WA; Instituto de Química, Universidade Federal de Uberlândia, Campus Santa Mônica, Uberlândia, MG, Brazil; Instituto de Ciências Exatas e da Terra, Campus Universitário do Araguaia, Universidade Federal do Mato Grosso, Pontal do Araguaia, MT, Brazil., Ramos LMS; Instituto de Química, Universidade Federal de Uberlândia, Campus Santa Mônica, Uberlândia, MG, Brazil., de Almeida AM; Departamento de Química, Universidade Federal de Juiz de Fora, Juiz de Fora, MG, Brazil., Tezuka DY; Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil., Lopes CD; Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil., Moreira MB; UNESP - Univ. Estadual Paulista, Institute of Chemistry, Araraquara, SP, Brazil; Departamento de Química, Universidade Estadual de Maringá, PR, Brazil., Zanetti RD; UNESP - Univ. Estadual Paulista, Institute of Chemistry, Araraquara, SP, Brazil., Netto AVG; UNESP - Univ. Estadual Paulista, Institute of Chemistry, Araraquara, SP, Brazil., Ferreira FB; Faculdades Associadas de Uberaba, Uberaba, MG, Brazil., de Oliveira RJ; Laboratório de Biofísica Teórica, Departamento de Física, Instituto de Ciências Exatas, Naturais e Educação, Universidade Federal do Triângulo Mineiro, Uberaba, MG, Brazil., Guedes GP; Instituto de Química, Universidade Federal Fluminense, Campus Valonguinho, Niterói, RJ, Brazil., de Albuquerque S; Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil., Silva JRL; Departamento de Química, Universidade Federal de Minas Gerais, Campus Pampulha, Belo Horizonte, MG, Brazil., Pereira-Maia EC; Departamento de Química, Universidade Federal de Minas Gerais, Campus Pampulha, Belo Horizonte, MG, Brazil., Resende JALC; Instituto de Ciências Exatas e da Terra, Campus Universitário do Araguaia, Universidade Federal do Mato Grosso, Pontal do Araguaia, MT, Brazil., de Almeida MV; Departamento de Química, Universidade Federal de Juiz de Fora, Juiz de Fora, MG, Brazil., Guerra W; Instituto de Química, Universidade Federal de Uberlândia, Campus Santa Mônica, Uberlândia, MG, Brazil. Electronic address: wendell.guerra@ufu.br.
Jazyk: angličtina
Zdroj: Journal of inorganic biochemistry [J Inorg Biochem] 2022 Dec; Vol. 237, pp. 111993. Date of Electronic Publication: 2022 Sep 09.
DOI: 10.1016/j.jinorgbio.2022.111993
Abstrakt: This work describes the synthesis, characterization and in vitro anticancer activity of two platinum(II) complexes of the type [Pt(L1) 2 (1,10-phen)] 1 and [Pt(L2) 2 (1,10-phen)] 2, where L1 = 5-heptyl-1,3,4-oxadiazole-2-(3H)-thione, L2 = 5-nonyl-1,3,4-oxadiazole-2-(3H)-thione and 1,10-phen = 1,10-phenanthroline. As to the structure of these complexes, the X-ray structural analysis of 1 indicates that the geometry around the platinum(II) ion is distorted square-planar, where two 5-alkyl-1,3,4-oxadiazol-2-thione derivatives coordinate a platinum(II) ion through the sulfur atom. A chelating bidentate phenanthroline molecule completes the coordination sphere. We tested these complexes in two breast cancer cell lines, namely, MCF-7 (a hormone responsive cancer cell) and MDA-MB-231 (triple negative breast cancer cell). In both cells, the most lipophilic platinum compound, complex 2, was more active than cisplatin, one of the most widely used anticancer drugs nowadays. DNA binding studies indicated that such complexes are able to bind to ct-DNA with K b values of 10 4  M -1 . According to data from dichroism circular and fluorescence spectroscopy, these complexes appear to bind to the DNA in a non-intercalative, probably via minor groove. Molecular docking followed by semiempirical simulations indicated that these complexes showed favorable interactions with the minor groove of the double helix of ct-DNA in an A-T rich region. Thereafter, flow cytometry analysis showed that complex 2 induced apoptosis and necrosis in MCF-7 cells.
Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest.
(Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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