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, -amino esters, amides, -amino amides, ethers, -amino ethers, inverse esters, and amides. These candidates were found to have high invitro potencies (COX-2 inhibition at 10m: 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 2b [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; Dicesaremannelli, Lorenzo; Biava, Mariangela. - In: CHEMMEDCHEM. - ISSN 1860-7179. - STAMPA. - 11:16(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

CONSALVI, SARA
;
POCE, Giovanna;RAGNO, Rino;SABATINO, MANUELA;BIAVA, Mariangela
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, -amino esters, amides, -amino amides, ethers, -amino ethers, inverse esters, and amides. These candidates were found to have high invitro potencies (COX-2 inhibition at 10m: 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 2b [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.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/891076
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