6-Substituted purines as ROCK inhibitors with anti-metastatic activity
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
31271944
DOI
10.1016/j.bioorg.2019.103005
PII: S0045-2068(18)31575-X
Knihovny.cz E-zdroje
- Klíčová slova
- Anti-metastatic activity, Melanoma, Protein kinase inhibitor, ROCK,
- MeSH
- inhibitory proteinkinas chemická syntéza farmakologie MeSH
- kinázy asociované s Rho antagonisté a inhibitory MeSH
- lidé MeSH
- molekulární struktura MeSH
- nádorové buněčné linie MeSH
- pohyb buněk účinky léků MeSH
- proliferace buněk účinky léků MeSH
- protinádorové látky chemická syntéza farmakologie MeSH
- puriny chemická syntéza farmakologie MeSH
- signální transdukce účinky léků MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- inhibitory proteinkinas MeSH
- kinázy asociované s Rho MeSH
- protinádorové látky MeSH
- puriny MeSH
- ROCK2 protein, human MeSH Prohlížeč
Rho-associated serine/threonine kinases (ROCKs) are principal regulators of the actin cytoskeleton that regulate the contractility, shape, motility, and invasion of cells. We explored the relationships between structure and anti-ROCK2 activity in a group of purine derivatives substituted at the C6 atom by piperidin-1-yl or azepan-1-yl groups. Structure-activity relationship (SAR) analyses suggested that anti-ROCK activity is retained, and may be further increased, by substitution of the parent compounds at the C2 atom or by expansion of the C6 side chain. These inhibitors of ROCK can reach effective concentrations within cells, as demonstrated by a decrease in phosphorylation of the ROCK target MLC, and by inhibition of the ROCK-dependent invasion of melanoma cells in the collagen matrix. Our study may be useful for further optimization of C6-substituted purine inhibitors of ROCKs and of other sensitive kinases identified by the screening of a broad panel of protein kinases.
Citace poskytuje Crossref.org
