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Design, Synthesis, and Anticancer Effect Studies of Iridium(III) Polypyridyl Complexes against SGC-7901 Cells.
Molecules ; 24(17)2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31466318
ABSTRACT
Three iridium(III) complexes ([Ir(Hppy)2(L)](PF6) (Hppy = 2-phenylpyridine, L = 5-nitrophenanthroline, NP), 1; 5-nitro-6-amino-phenanthroline (NAP), 2; and 5,6-diamino-phenanthroline (DAP) 3 were synthesized and characterized. The cytotoxicities of Ir(III) complexes 1-3 against cancer cell lines SGC-7901, A549, HeLa, Eca-109, HepG2, BEL-7402, and normal NIH 3T3 cells were investigated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide (MTT) method. The results showed that the three iridium(III) complexes had moderate in vitro anti-tumor activity toward SGC-7901 cells with IC50 values of 3.6 ± 0.1 µM for 1, 14.1 ± 0.5 µM for 2, and 11.1 ± 1.3 µM for 3. Further studies showed that 1-3 induce cell apoptosis/death through DNA damage, cell cycle arrest at the S or G0/G1 phase, ROS elevation, increased levels of Ca2+, high mitochondrial membrane depolarization, and cellular ATP depletion. Transwell and Colony-Forming assays revealed that complexes 1-3 can also effectively inhibit the metastasis and proliferation of tumor cells. These results demonstrate that 1-3 induce apoptosis in SGC-7901 cells through ROS-mediated mitochondrial damage and DNA damage pathways, as well as by inhibiting cell invasion, thereby exerting anti-tumor cell proliferation activity in vitro.
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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Piridinas / Neoplasias Gástricas / Espécies Reativas de Oxigênio / Complexos de Coordenação / Irídio Limite: Animais / Humanos Idioma: Inglês Assunto da revista: Biologia Ano de publicação: 2019 Tipo de documento: Artigo País de afiliação: China