Herein we report the synthesis, biological evaluation, and docking analysis of a class of cyclooxygenase-2 (COX-2) inhibitors with nitric oxide (NO)-releasing properties. In an earlier study, a number of selective COX-2 inhibitors/NO donors were developed by conjugating a diarylpyrrole scaffold endowed with selective COX-2 inhibitory properties with various nitrooxyalkyl side chains such as esters, α-amino esters, amides, α-amino amides, ethers, β-amino ethers, inverse esters, and amides. These candidates were found to have high in vitro potencies (COX-2 inhibition at 10 μm: ≥96 %), great efficacy in determining NO-vasorelaxing responses, and good antinociceptive activity in an abdominal writhing test. Among the compounds synthesized in the present work, derivative 2 b [2-(2-(1-(3-fluorophenyl)-2-methyl-5-(4-sulfamoylphenyl)-1H-pyrrol-3-yl)acetamido)ethyl nitrate] showed particularly outstanding activity, with efficacy similar to that of celecoxib even at very low concentrations.

A Series of COX-2 Inhibitors Endowed with NO-Releasing Properties: Synthesis, Biological Evaluation, and Docking Analysis / Consalvi, Sara; Poce, Giovanna; Ragno, Rino; Sabatino, Manuela; Lamotta, Concettina; Sartini, Stefania; Calderone, Vincenzo; Martelli, Alma; Ghelardini, Carla; DI CESARE MANNELLI, Lorenzo; Biava, Mariangela. - In: CHEMMEDCHEM. - ISSN 1860-7179. - STAMPA. - 11:(2016), pp. 1804-1811. [10.1002/cmdc.201600086]

A Series of COX-2 Inhibitors Endowed with NO-Releasing Properties: Synthesis, Biological Evaluation, and Docking Analysis

GHELARDINI, CARLA;DI CESARE MANNELLI, LORENZO;
2016

Abstract

Herein we report the synthesis, biological evaluation, and docking analysis of a class of cyclooxygenase-2 (COX-2) inhibitors with nitric oxide (NO)-releasing properties. In an earlier study, a number of selective COX-2 inhibitors/NO donors were developed by conjugating a diarylpyrrole scaffold endowed with selective COX-2 inhibitory properties with various nitrooxyalkyl side chains such as esters, α-amino esters, amides, α-amino amides, ethers, β-amino ethers, inverse esters, and amides. These candidates were found to have high in vitro potencies (COX-2 inhibition at 10 μm: ≥96 %), great efficacy in determining NO-vasorelaxing responses, and good antinociceptive activity in an abdominal writhing test. Among the compounds synthesized in the present work, derivative 2 b [2-(2-(1-(3-fluorophenyl)-2-methyl-5-(4-sulfamoylphenyl)-1H-pyrrol-3-yl)acetamido)ethyl nitrate] showed particularly outstanding activity, with efficacy similar to that of celecoxib even at very low concentrations.
2016
11
1804
1811
Consalvi, Sara; Poce, Giovanna; Ragno, Rino; Sabatino, Manuela; Lamotta, Concettina; Sartini, Stefania; Calderone, Vincenzo; Martelli, Alma; Ghelardini, Carla; DI CESARE MANNELLI, Lorenzo; Biava, Mariangela
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1065326
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