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10.1080/14756366.2018.1490732 http://scihub22266oqcxt.onion/10.1080/14756366.2018.1490732 C6060383!6060383 !30044647     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=30044647 &cmd=llinks): Failed to open stream: HTTP request failed! 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Synthesis and pharmacological evaluation of novel isoquinoline N-sulphonylhydrazones designed as ROCK inhibitors |pdf=|usr=}}{{30044647 }} gab.com Text Synthesis and pharmacological evaluation of novel isoquinoline N-sulphonylhydrazones designed as ROCK inhibitors JO: J Enzyme Inhib Med Chem http://www.kidney.de/pget.php?&tw=1&pmid=30044647 #FOAvip 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-? 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 IC(50) values of 3.1 and 3.8?µM 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. Twit Text FOAVip Synthesis and pharmacological evaluation of novel isoquinoline N-sulphonylhydrazones designed as ROCK inhibitors ????J Enzyme Inhib Med Chem http://www.kidney.de/pget.php?&tw=1&pmid=30044647 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=30044647 #FOAvip English Wikipedia <ref>{{Cite pmid|30044647 }}</ref> Synthesis and pharmacological evaluation of novel isoquinoline N-sulphonylhydrazones designed as ROCK inhibitors #MMPMID30044647 Oliveira RG ; Guerra FS ; Mermelstein CDS ; Fernandes PD ; Bastos ITS ; Costa FN ; Barroso RCR ; Ferreira FF ; Fraga CAM J Enzyme Inhib Med Chem 2018[Dec]; 33 (1 ): 1181-1193 PMID30044647 show ga 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-? 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 IC(50) values of 3.1 and 3.8?µM 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. |1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/analogs & derivatives/chemistry/pharmacology [MESH] |Animals [MESH] |Cell Line, Tumor [MESH] |Female [MESH] |Humans [MESH] |Hydrazones/chemical synthesis/*chemistry/pharmacology [MESH] |Isoquinolines/*chemistry [MESH] |Models, Molecular [MESH] |Powder Diffraction [MESH] |Protein Kinase Inhibitors/*chemical synthesis/*pharmacology [MESH] |Spectrum Analysis/methods [MESH]Synthesis and pharmacological evaluation of novel isoquinoline N-sul(epmc).pdf DeepDyve Pubget Overpricing