Screening of NOS activity and selectivity of newly synthesized acetamidines using RP-HPLC

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• 作者：Marialuigia Fantacuzzi ; ^{marialuigia.fantacuzzi@unich.it" class="auth_mail" title="E-mail the corresponding author} ; Cristina Maccallini ; Mauro Di Matteo ; Alessandra Ammazzalorso ; Isabella Bruno ; Barbara De Filippis ; Letizia Giampietro ; Adriano Mollica ; Rosa Amoroso
• 关键词：High-performance liquid chromatography ; Nitric Oxide Synthase inhibitor ; Acetamidine ; Fluorescence detection ; OPA/NAC derivatization
• 刊名：Journal of Pharmaceutical and Biomedical Analysis
• 出版年：2016
• 出版时间：20 February 2016
• 年：2016
• 卷：120
• 期：Complete
• 页码：419-424
• 全文大小：625 K

文摘

Nitric Oxide Synthase (NOS) inhibitors could play a powerful role in inflammatory and neurodegenerative diseases. In this work, novel acetamidine derivatives of NOS were synthesized and the inhibitor activity was evalued. To screen the activity and selectivity, the l-citrulline residue, after the enzymatic NOS assay, was derivatized with o-phthaldialdehyde/N-acetyl cysteine (OPA/NAC) and then evaluated by RP-HPLC method with fluorescence detection.

All compounds did not affect the activity of endothelial and neuronal isoforms, while nine of them possessed a percentage of iNOS activity at 10 μM lower than 50%, and were selected for IC₅₀ evaluation. Among them, a compound emerged as a very potent (IC₅₀ of 53 nM) and selective iNOS inhibitor.