6-​Bromo-​quinazolinone derivs. were prepd. and evaluated for the ability to inhibit cyclooxygenase-​2 (COX-​2)​. An extensive structure-​activity relationship work was carried out, thus some potent and selective COX-​2 inhibitors were identified. The key compd. isothiocyanate was prepd. through a simple and ecol. method using di-​2-​pyridyl thionocarbonate in substitution of the thiophosgene, a potential air pollutant. The cyclization reaction of intermediate derivs. was developed through the methods reporting by Wamhoff. The anti-​inflammatory activity of the derivs. was evaluated by detg. (by Western blot) the expression of cyclooxygenase (COX)​-​2, of inducible NO synthase (iNOS) and of intercellular adhesion mol.-​1 (ICAM-​1)​. The biol. assays showed that some of the derivs. act as potent inhibitors of COX-​2, iNOS, and ICAM-​1 expression in human keratinocytes NCTC-​2544 cells. This work showed that the new derivs. could be used as a novel class of anti-​inflammatory agents.

Synthesis, structure-​activity relationships, and bioactivity evaluation of 6-​bromo-​quinazolinone derivatives

BARONE, MARIARITA;PISTARA', Venerando;FRASCA, GIUSEPPINA;CATALFO, ALFIO;SANTAGATI, Andrea
2015-01-01

Abstract

6-​Bromo-​quinazolinone derivs. were prepd. and evaluated for the ability to inhibit cyclooxygenase-​2 (COX-​2)​. An extensive structure-​activity relationship work was carried out, thus some potent and selective COX-​2 inhibitors were identified. The key compd. isothiocyanate was prepd. through a simple and ecol. method using di-​2-​pyridyl thionocarbonate in substitution of the thiophosgene, a potential air pollutant. The cyclization reaction of intermediate derivs. was developed through the methods reporting by Wamhoff. The anti-​inflammatory activity of the derivs. was evaluated by detg. (by Western blot) the expression of cyclooxygenase (COX)​-​2, of inducible NO synthase (iNOS) and of intercellular adhesion mol.-​1 (ICAM-​1)​. The biol. assays showed that some of the derivs. act as potent inhibitors of COX-​2, iNOS, and ICAM-​1 expression in human keratinocytes NCTC-​2544 cells. This work showed that the new derivs. could be used as a novel class of anti-​inflammatory agents.
2015
Quinazolinone; Synthesis; Anti-inflammatory
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/49019
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