Nido-Dicarbaborate Induces Potent and Selective Inhibition of Cyclooxygenase-2.

ABSTRACT: Carbaboranes are increasingly studied as pharmacophores, particularly as replacements for aromatic systems. However, especially ortho-carbaborane is prone to degradation of the cluster, which hampers biological application. This study demonstrates that deboronation of the cluster may not only lead to a more active analogue, but can also improve the solubility and stability of a carbaborane-containing inhibitor. Notably, introduction of a nido-dicarbaborate cluster into the cyclooxygenase (COX) inhibitor indomethacin results in remarkably increased inhibitory potency and selectivity for COX-2 relative to the respective phenyl analogue. The first crystal structure of a carbaborane-containing inhibitor bound to COX-2 further reveals a novel binding mode for the inhibitor that is strikingly di

SUBMITTER: Neumann W 

PROVIDER: S-EPMC4900168 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature