Síntese e investigação do potencial citotóxico de compostos de ouro(III) com hidrazonas e bis(hidrazonas) derivadas de isoniazida

• Autor(a) principal: Firmino, Gisele dos Santos Silva
• Data de Publicação: 2019
• Outros Autores: [e-mail]
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/18864
• topic: Isoniazid; Hydrazone; Bis(hydrazone); Gold(III)complex; Cytotoxity action; Hidrazonas; Isoniazida; Bis(hidrazona); Complexo de ouro(III); Atividade citotóxica; CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA INORGANICA

About 29,5 million cancer new cases are expected in the worldwide in 2040. such perspective boosts a serie of efforts preventing disease and optimizing treatments, make it more efficients by promoting better life quality to pacientes and incresed their cure chances. in this scenario, medicinal inorganic chemistry studies contributed to compounds obtention with clinical use because of anticancer action proved - cisplatina case. coordination of metal ions to organic molecules with a wide pharmacological spectra, proved to be one of the ways to follow to obtain metallopharmaceutical with interesting cytotoxic potential. Thus, in this present work we synthetized N-acyl hydrazones and bis(N-acyl hydrazones) derived from isoniazid and their gold(III) complexes in order to investigate their cytotoxic potential against the tumor cell lines: HL60 (wild type human promyelocytic leukemia), MCF7 and MDA‒MB‒293 (human breast carcinoma), HCT116 (human colorectal carcinoma) and PC─3 (human prostate cancer). Chemical structures were elucidated by differents techniques as melting point, elemental analysis; infrared (IR), electronic and nuclear magnetic resonance (NMR) spectroscopy; conductivimetry and mass spectrometry. Eight isoniazid derivatives were obtained: Hpcih (L01), Hapih (L02), Hbpih (L03), Hpamih (L04), H2ginh (L05), H2pinh (L06) and H2pamih (L07) are described in literature and H2bpinh (L08), is new. Six gold(III) complexes with this ligands are inedited: [Au(H3pcih)Cl3]Cl2∙2H2O (C01), [Au(H3bpih)Cl3]Cl2∙2H2O (C03), [Au(pamih)Cl2]‧½CH3OH (C04), Au(H2ginh)Cl2]Cl‧½CH3OH (C05), [Au(Hpinh)OH]Cl (C06) and [Au(H2bpinh)Cl2]Cl‧½CH3OH (C08). Hapih was the most active N-acyl hydrazone to HL-60, MCF-7, PC-3 and HCT-116 cell lines reducing cell viabillity more than 50 % to HL-60 and showed more activity than reference farmacs. C03 is highly cytotoxic to HL-60 and HCT-116 cells, IC50 values are 2.4 ± 2.17 and 2.4 ± 1.3 μmol L─1, respectively. Furthermore, C03 is more potent than HAuCl4‧3H2O and etoposide against MDA-MB-231, MCF-7 and HCT-116 cells, respectively. Its IC90 promotes a zero survival fraction in HCT-116 cells in the clonogenicity assay. According to investigation of action mechanism for C03, the complex may not induce apoptosis cell death. C03 proved to be a compound with interesting cytotoxic action in vitro for further study of its pharmacological potential.