Dataset Information

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 different from that of indomethacin. These results indicate that nido-dicarbaborate is a promising pharmacophore that exhibits properties which are also highly beneficial for its introduction into other inhibitor classes.

SUBMITTER: Neumann W

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

REPOSITORIES: biostudies-literature

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

Neumann Wilma W Xu Shu S Sárosi Menyhárt B MB Scholz Matthias S MS Crews Brenda C BC Ghebreselasie Kebreab K Banerjee Surajit S Marnett Lawrence J LJ Hey-Hawkins Evamarie E

ChemMedChem 20150618 2

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) i ...[more]

PMID: 26088701

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Dataset Information

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

Publications

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

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