Discovery of pyrrole-indoline-2-ones as Aurora kinase inhibitors with a different inhibition profile.
J Med Chem
; 53(16): 5929-41, 2010 Aug 26.
Article
in En
| MEDLINE
| ID: mdl-20681538
ABSTRACT
A series of pyrrole-indolin-2-ones were synthesized, and their inhibition profile for Aurora kinases was studied. The potent compound 33 with phenylsulfonamido at the C-5 position and a carboxyethyl group at the C-3' position selectively inhibited Aurora A over Aurora B with IC50 values of 12 and 156 nM, respectively. Replacement of the carboxyl group with an amino group led to compound 47, which retained the activity for Aurora B and lost activity for Aurora A (IC50=2.19 microM). Computation modeling was used to address the different inhibition profiles of 33 and 47. Compounds 47 and 36 (the ethyl ester analogue of 33) inhibited the proliferation of HCT-116 and HT-29 cells and suppressed levels of the phosphorylated substrates of Aurora A and Aurora B in the Western blots.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyrroles
/
Protein Serine-Threonine Kinases
/
Indoles
/
Antineoplastic Agents
Limits:
Humans
Language:
En
Journal:
J Med Chem
Journal subject:
QUIMICA
Year:
2010
Document type:
Article