The marine natural-derived inhibitors of glycogen synthase kinase-3beta phenylmethylene hydantoins: In vitro and in vivo activities and pharmacophore modeling.

ABSTRACT: The Red Sea sponge Hemimycale arabica afforded the known (Z)-5-(4-hydroxybenzylidene)-hydantoin (1). This natural phenylmethylene hydantoin (PMH) 1 and the synthetic (Z)-5-(4-(ethylthio)benzylidene)-hydantoin (2) showed potent in vitro and in vivo anti-growth and anti-invasive properties against PC-3M prostate cancer cells in MTT, spheroid disaggregation, and in mice models. To explore a possible molecular target of PMHs, the most potent synthetic analogue 2 has been virtually screened against various protein kinases. Molecular modeling study has shown that 2 can be successfully docked within the binding pocket of glycogen synthase kinase-3beta (GSK-3beta) similar to the well-known GSK-3beta inhibitor I-5. Several PMHs showed potent in vitro GSK-3beta inhibitory activity with an IC(50) ran

SUBMITTER: Khanfar MA 

PROVIDER: S-EPMC2743475 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature