Synthesis and evaluation of novel pyrazole derivatives for cytotoxic activity

• Autor(a) principal: Carreira, Ana Rita Futre
• Data de Publicação: 2018
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10773/24248
• topic: Hydroxyphenylstyrylpyrazoles; Ruthenium complexes; Cytotoxic activity

The growing number of cancer patients worldwide has led the scientific community to strengthen research efforts in this field. The development of novel drug candidates for cancer treatment has been largely studied. Among these, pyrazoles derivatives are a promising class for their wide range of pharmacological activities, including antitumoral action. This work describes the preparation of (E)-3(5)-(2-hydroxyphenyl)-4-styryl-1H-pirazole derivatives, either by glycosylation reactions or by the formation of ruthenium trithiacyclononane complexes. The new compounds aim at having antitumoral activity. Full characterization of the compounds is carried out by NMR 1D (1H and 13C) and 2D (HSQC, HMBC, COSY and NOESY) spectroscopies and by mass spectrometry. The new ruthenium-pyrazoles are also studied by infrared spectroscopy. Whenever appropriate, the purity of the synthesized compounds is evaluated by melting point measurements. The compounds are evaluated against a gastric cancer cell line (AGS) and against a lung fibroblast cell line (MRC-5) to roughly assess their selectivity. The most potent compound is the ruthenium complex with the pyrazole having a -para-OCH3 substituted styryl. This compound features an IC50 value of 18.3 μM against the cancer cell line AGS and an IC50 value of 62.2 μM on the healthy cell line MRC-5. Furthermore, the selectivity of this complex with this ligand is higher in comparison to that of ligand alone