3-O-methylthespesilactam, a new small-molecule anticancer pan-JAK inhibitor against A2058 human melanoma cells.
Biochem Pharmacol
; 86(10): 1411-8, 2013 Nov 15.
Article
en En
| MEDLINE
| ID: mdl-24021352
ABSTRACT
Natural product-inspired discovery of new drug leads plays a key role in drug development. Recently, small-molecule JAK inhibitors have been pursued for the development of anticancer therapeutics. However, most of these inhibitors reported up to now are multi-nitrogen polycyclic aromatic heterocycles. Undoubtedly, the discovery of new types of promising JAK-inhibitory leads is pivotal for JAK inhibitor-based anticancer drug development. Herein we report an unprecedented sesquiterpenoid-alkaloid named thespesilactam, containing a benzo[cd]indole scaffold, from the heartwood of the Portia tree, Thespesia populnea. Its 3-O-Me product, i.e. 8-hydroxy-5-isopropyl-3-methoxy-7-methylbenzo[cd]indol-2(1H)-one, named 3-O-methylthespesilactam, of which the structure was identified by NMR investigations and single-crystal X-ray diffraction analysis, was discovered as a new type of small-molecule anticancer pan-JAK inhibitor against A2058 human melanoma cells, and selective and potent inhibitor of JAK1 and TYK2.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Sesquiterpenos
/
Alcaloides
/
Quinasas Janus
/
Antineoplásicos
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Biochem Pharmacol
Año:
2013
Tipo del documento:
Article