A small library of boron-cluster- and metallacarborane-cluster-based ligands was designed, prepared, and tested for isoform-selective activation or inhibition of the three nitric oxide synthase isoforms. On the basis of the concept of creating a hydrophobic analogue of a natural substrate, a stable and nontoxic basic boron cluster system, previously used for boron neutron capture therapy, was modified by the addition of positively charged moieties to its periphery, providing hydrophobic and nonclassical hydrogen bonding interactions with the protein. Several of these compounds show efficacy for inhibition of NO synthesis with differential effects on the various nitric oxide synthase isoforms.

• MeSH
• Models, Chemical MeSH
• Cobalt chemistry   MeSH
• Humans MeSH
• Molecular Structure MeSH
• Organometallic Compounds chemical synthesis   pharmacology   MeSH
• Protein Isoforms MeSH
• Boron Compounds chemical synthesis   pharmacology   MeSH
• Nitric Oxide Synthase antagonists & inhibitors   metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Names of Substances
• Cobalt MeSH
• Organometallic Compounds MeSH
• Protein Isoforms MeSH
• Boron Compounds MeSH
• Nitric Oxide Synthase MeSH