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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Synthesis and pharmacological evaluation of novel isoquinoline N-sulphonylhydrazones designed as ROCK inhibitors

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de Oliveira, Ramon Guerra [1, 2] ; Guerra, Fabiana Selos [1, 3] ; Mermelstein, Claudia dos Santos [4] ; Fernandes, Patricia Dias [1, 3] ; de Sena Bastos, Isadora Tairinne [5] ; Costa, Fanny Nascimento [6] ; Rodrigues Barroso, Regina Cely [5] ; Ferreira, Fabio Furlan [6] ; Manssour Fraga, Carlos Alberto [1, 2]
Total Authors: 9
[1] Univ Fed Rio de Janeiro, Inst Ciencias Biomed, Programa Posgrad Farmacol & Quim Med, Rio De Janeiro - Brazil
[2] Univ Fed Rio de Janeiro, Inst Ciencias Biomed, Lab Avaliacao & Sintese Subst Bioat LASSBio, Rio De Janeiro - Brazil
[3] Univ Fed Rio de Janeiro, Inst Ciencias Biomed, Lab Farmacol Dor & Inflamacao, Rio De Janeiro - Brazil
[4] Univ Fed Rio de Janeiro, Inst Ciencias Biomed, Lab Diferenciacao Muscular, Rio De Janeiro - Brazil
[5] Univ Estado Rio de Janeiro, Inst Fis, Rio De Janeiro - Brazil
[6] UFABC, CCNH, Sao Paulo - Brazil
Total Affiliations: 6
Document type: Journal article
Source: Journal of Enzyme Inhibition and Medicinal Chemistry; v. 33, n. 1, p. 1181-1193, JUL 25 2018.
Web of Science Citations: 1

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)

FAPESP's process: 15/26233-7 - Synthesis and structural characterization of cocrystals for application as sunscreen and antioxidants of topical use
Grantee:Fabio Furlan Ferreira
Support type: Regular Research Grants