| Texto completo | |
| Autor(es): |
de Oliveira, Ramon Guerra
;
Guerra, Fabiana Selos
;
Mermelstein, Claudia dos Santos
;
Fernandes, Patricia Dias
;
de Sena Bastos, Isadora Tairinne
;
Costa, Fanny Nascimento
;
Rodrigues Barroso, Regina Cely
;
Ferreira, Fabio Furlan
;
Manssour Fraga, Carlos Alberto
Número total de Autores: 9
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Journal of Enzyme Inhibition and Medicinal Chemistry; v. 33, n. 1, p. 13-pg., 2018-07-25. |
| Resumo | |
In this study, we synthesized a new congener series of N-sulphonylhydrazones designed as candidate ROCK inhibitors using the molecular hybridization of the clinically approved drug fasudil (1) and the IKK-beta inhibitor LASSBio-1524 (2). Among the synthesized compounds, the N-methylated derivative 11 (LASSBio-2065) showed the best inhibitory profile for both ROCK isoforms, with IC50 values of 3.1 and 3.8 mu M for ROCK1 and ROCK2, respectively. Moreover, these compounds were also active in the scratch assay performed in human breast cancer MDA-MB 231 cells and did not display toxicity in MTT and LDH assays. Molecular modelling studies provided insights into the possible binding modes of these N-sulphonylhydrazones, which present a new molecular architecture capable of being optimized and developed as therapeutically useful ROCK inhibitors. (AU) | |
| Processo FAPESP: | 15/26233-7 - Síntese e caracterização estrutural de cocristais para aplicações em protetores solares e antioxidantes de uso tópico |
| Beneficiário: | Fabio Furlan Ferreira |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |