title: A Series of COX-2 Inhibitors Endowed with NO-Releasing Properties: Synthesis, Biological Evaluation, and Docking Analysis.
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.
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, Piazzale A. Moro 5, 00185, Roma, Italy. sara.consalvi@uniroma1.it.
authors.forename: Sara
authors.initials: S
authors.lastname: Consalvi
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, Piazzale A. Moro 5, 00185, Roma, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Poce
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, Piazzale A. Moro 5, 00185, Roma, Italy.
authors.forename: Rino
authors.initials: R
authors.lastname: Ragno
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, Piazzale A. Moro 5, 00185, Roma, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Sabatino
authors.affiliation: Dipartimento di Farmacia, Università di Pisa, via Bonanno Pisano 6, 56126, Pisa, Italy.
authors.forename: Concettina
authors.initials: C
authors.lastname: La Motta
authors.affiliation: Dipartimento di Farmacia, Università di Pisa, via Bonanno Pisano 6, 56126, Pisa, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Sartini
authors.affiliation: Dipartimento di Farmacia, Università di Pisa, via Bonanno Pisano 6, 56126, Pisa, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Calderone
authors.affiliation: Dipartimento di Farmacia, Università di Pisa, via Bonanno Pisano 6, 56126, Pisa, Italy.
authors.forename: Alma
authors.initials: A
authors.lastname: Martelli
authors.affiliation: Dipartimento di Neurologia Psicologia, Area del Farmaco e Salute del Bambino, Università degli Studi di Firenze, Viale G. Pieraccini 6, 50139, Firenze, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Ghelardini
authors.affiliation: Dipartimento di Neurologia Psicologia, Area del Farmaco e Salute del Bambino, Università degli Studi di Firenze, Viale G. Pieraccini 6, 50139, Firenze, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Di Cesare Mannelli
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, Piazzale A. Moro 5, 00185, Roma, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Biava
mesh_terms: D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D051546:Cyclooxygenase 2
keywords: CINODs; COX-2 inhibitors; drug discovery; inflammation; pharmacodynamics