Priam Villalonga, Silvia Fernández de Mattos, Guillem Ramis, Antònia Obrador-Hevia, Angel Sampedro, Carmen Rotger, Antoni Costa
Institut Universitari d'Investigació en Ciències de la Salut, Universitat de les Illes Balears, Carretera Valldemossa km 7.5, Spain.
ChemMedChem 2012 AugWe report the synthesis and biological evaluation of a new series of oligosquaramide-based macrocycles as anticancer agents. Compound 7, considered as representative of this series, exhibited significant antiproliferative activity against the NCI-60 human tumor cell line panel, with IC(50) values ranging from 1 to 10 μM. The results show that sensitivity to cyclosquaramides is clearly dependent on cell type, underscoring a degree of biological selectivity. The observed antiproliferative effects appear to be related to deregulation of protein phosphorylation, as compounds 7 and 8 are effective inhibitors of several important kinases such as ABL1, CDK4, CHK1, PKC, c-MET, and FGFR, among others. The corresponding acyclic oligosquaramides and smaller cyclosquaramides did not show antitumor activity, suggesting that a macrocyclic structure with minimal molecular size plays a key role in the observed antitumor activity. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Priam Villalonga, Silvia Fernández de Mattos, Guillem Ramis, Antònia Obrador-Hevia, Angel Sampedro, Carmen Rotger, Antoni Costa. Cyclosquaramides as kinase inhibitors with anticancer activity. ChemMedChem. 2012 Aug;7(8):1472-80
PMID: 22777958
View Full Text