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

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• 作者：Robert Kapl谩nek ; Pavel Mart谩sek ; Bohum铆r Gr眉ner ; Satya Panda ; Jakub Rak ; Bettie Sue Siler Masters ; Vladim铆r Kr谩l ; Linda J. Roman
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：November 26, 2012
• 年：2012
• 卷：55
• 期：22
• 页码：9541-9548
• 全文大小：378K
• 年卷期：v.55,no.22(November 26, 2012)
• ISSN：1520-4804

文摘

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.