title: Screening of NOS activity and selectivity of newly synthesized acetamidines using RP-HPLC.
abstract: 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 10μM lower than 50%, and were selected for IC50 evaluation. Among them, a compound emerged as a very potent (IC50 of 53nM) and selective iNOS inhibitor.
authors.affiliation: Dipartimento di Farmacia, Università degli Studi "G. d'Annunzio", Chieti, Italy. Electronic address: marialuigia.fantacuzzi@unich.it.
authors.forename: Marialuigia
authors.initials: M
authors.lastname: Fantacuzzi
authors.affiliation: Dipartimento di Farmacia, Università degli Studi "G. d'Annunzio", Chieti, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Maccallini
authors.affiliation: Dipartimento di Farmacia, Università degli Studi "G. d'Annunzio", Chieti, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Di Matteo
authors.affiliation: Dipartimento di Farmacia, Università degli Studi "G. d'Annunzio", Chieti, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ammazzalorso
authors.affiliation: Dipartimento di Farmacia, Università degli Studi "G. d'Annunzio", Chieti, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Bruno
authors.affiliation: Dipartimento di Farmacia, Università degli Studi "G. d'Annunzio", Chieti, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: De Filippis
authors.affiliation: Dipartimento di Farmacia, Università degli Studi "G. d'Annunzio", Chieti, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Giampietro
authors.affiliation: Dipartimento di Farmacia, Università degli Studi "G. d'Annunzio", Chieti, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Mollica
authors.affiliation: Dipartimento di Farmacia, Università degli Studi "G. d'Annunzio", Chieti, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Amoroso
mesh_terms: D000578:Amidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000032:analysis* / Q000493:pharmacokinetics; D052247:Nitric Oxide Synthase Type II / Q000032:analysis* / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000578:Amidines; D004791:Enzyme Inhibitors; D052247:Nitric Oxide Synthase Type II; C023731:acetamidine
keywords: Acetamidine; Fluorescence detection; High-performance liquid chromatography; Nitric Oxide Synthase inhibitor; OPA/NAC derivatization