Nitric Oxide Synthases Activation and Inhibition by Metallacarborane-Cluster-Based Isoform-Specific Affectors

0383651 - ÚACH 2013 RIV US eng J - Journal Article
Kaplánek, R. - Martásek, P. - Grüner, Bohumír - Panda, S. - Rak, J. - Masters, B.S. - Král, V. - Roman, L.J.
Nitric Oxide Synthases Activation and Inhibition by Metallacarborane-Cluster-Based Isoform-Specific Affectors.
Journal of Medicinal Chemistry. Roč. 55, č. 22 (2012), s. 9541-9548. ISSN 0022-2623. E-ISSN 1520-4804
R&D Projects: GA AV ČR IAAX00320901
Institutional support: RVO:61388980
Keywords : neutron-capture therapy * dicarba-closo-dodecaborane * medicinal chemistry
Subject RIV: CA - Inorganic Chemistry
Impact factor: 5.614, year: 2012

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.
Permanent Link: http://hdl.handle.net/11104/0216650