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.File | Dimensione | Formato | |
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