Adamantyl arotinoids that inhibit IκB kinase α and IκB kinase β.

ABSTRACT: A series of analogues of the adamantyl arotinoid (AdAr) chalcone MX781 with halogenated benzyloxy substituents at C2' and heterocyclic derivatives replacing the chalcone group were found to inhibit IκBα kinase α (IKKα) and IκBα kinase β (IKKβ) activities. The growth inhibitory capacity of some analogues against Jurkat T cells as well as prostate carcinoma (PC-3) and chronic myelogenous leukemia (K562) cells, which contain elevated basal IKK activity, correlates with the induction of apoptosis and increased inhibition of recombinant IKKα and IKKβ in vitro, pointing toward inhibition of IKK/NFκB signaling as the most likely target of the anticancer activities of these AdArs. While the chalcone functional group present in many dietary compounds has been shown to mediate interactions with IKKβ

SUBMITTER: Lorenzo P 

PROVIDER: S-EPMC3892996 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature