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Selective Acetamidine-Based Nitric Oxide Synthase Inhibitors: Synthesis, Docking, and Biological Studies.

ABSTRACT: N-[(3-Aminomethyl)benzyl]acetamidine derivatives were synthesized and in vitro evaluated as inhibitors of the inducible isoform of nitric oxide synthase (iNOS). Because of the high potency of action and the excellent selectivity over the endothelial nitric oxide synthase (eNOS), compound 10 was ex vivo evaluated on isolated and perfused resistance arteries. The results confirm that compound 10 selectively inhibits the iNOS, without affecting the endothelial isoform. The outcome of the docking studies showed that the hydrophobic interaction is the driving force of the binding process, especially for iNOS, where the binding pocket is characterized by a significant lipophilic region.

SUBMITTER: Maccallini C

PROVIDER: S-EPMC4468396 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Selective Acetamidine-Based Nitric Oxide Synthase Inhibitors: Synthesis, Docking, and Biological Studies.

Maccallini Cristina C Montagnani Monica M Paciotti Roberto R Ammazzalorso Alessandra A De Filippis Barbara B Di Matteo Mauro M Di Silvestre Sara S Fantacuzzi Marialuigia M Giampietro Letizia L Potenza Maria A MA Re Nazzareno N Pandolfi Assunta A Amoroso Rosa R

ACS medicinal chemistry letters 20150428 6

N-[(3-Aminomethyl)benzyl]acetamidine derivatives were synthesized and in vitro evaluated as inhibitors of the inducible isoform of nitric oxide synthase (iNOS). Because of the high potency of action and the excellent selectivity over the endothelial nitric oxide synthase (eNOS), compound 10 was ex vivo evaluated on isolated and perfused resistance arteries. The results confirm that compound 10 selectively inhibits the iNOS, without affecting the endothelial isoform. The outcome of the docking st ...[more]

PMID: 26101565

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