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

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Abstract

6-Bromo-quinazolinone derivatives were prepared 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 compound isothiocyanate was prepared through a simple and ecological method using di-2-pyridyl thionocarbonate in substitution of the thiophosgene, a potential air pollutant. The cyclization reaction of intermediate derivatives was developed through the methods reporting by Wamhoff. The anti-inflammatory activity of the derivatives (5–12) was evaluated by determining (by Western blot) the expression of cyclooxygenase (COX)-2, of inducible NO synthase (iNOS) and of intercellular adhesion molecule-1 (ICAM-1). The biological assays showed that the derivatives 7, 9, 10, 12 act as potent inhibitors of COX-2, iNOS, and ICAM-1 expression in human keratinocytes NCTC-2544 cells. This work showed that the new derivatives could be used as a novel class of anti-inflammatory agents.

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  1. Dipartimento di Scienze del Farmaco, Università di Catania, Viale A. Doria 6, 95125, Catania, Italy

    Mariarita Barone, Venerando Pistarà, Clio Noto, Maria Scribano & Andrea Santagati

  2. Dipartimento di Scienze Chimiche, Sezione di Fotochimica, Università di Catania, Viale A. Doria 6, 95125, Catania, Italy

    Alfio Catalfo

  3. Dipartimento di Scienze Bio-mediche, Sezione di Fisiologia, Università di Catania, Viale A. Doria 6, 95125, Catania, Italy

    Giuseppina Frasca

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  1. Mariarita Barone
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  2. Venerando Pistarà
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Correspondence to Mariarita Barone.

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Barone, M., Pistarà, V., Frasca, G. et al. Synthesis, structure–activity relationships, and bioactivity evaluation of 6-bromo-quinazolinone derivatives. Med Chem Res 24, 2461–2475 (2015). https://doi.org/10.1007/s00044-014-1311-7

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