Pharmacological Evaluation and Preliminary Pharmacokinetics Studies of a New Diclofenac Prodrug without Gastric Ulceration Effect

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dos Santos, Jean Leandro ; Moreira, Vanessa ; Campos, Michel Leandro ; Chelucci, Rafael Consolin ; Barbieri, Karina Pereira ; Maggio de Castro Souto, Pollyana Cristina ; Matsubara, Marcio Hideki ; Teixeira, Catarina ; Bosquesi, Priscila Longhin ; Peccinini, Rosangela Goncalves ; Chin, Chung Man

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 13, n. 11, p. 16-pg., 2012-11-01.

Abstract

Long-term nonsteroidal anti-inflammatory drugs (NSAIDs) therapy has been associated with several adverse effects such as gastric ulceration and cardiovascular events. Among the molecular modifications strategies, the prodrug approach is a useful tool to discover new safe NSAIDs. The 1-(2,6-dichlorophenyl)indolin-2-one is a diclofenac prodrug which demonstrated relevant anti-inflammatory properties without gastro ulceration effect. In addition, the prodrug decreases PGE(2) levels, COX-2 expression and cellular influx into peritoneal cavity induced by carrageenan treatment. Preliminary pharmacokinetic studies have shown in vivo bioconversion of prodrug to diclofenac. This prodrug is a new nonulcerogenic NSAID useful to treat inflammatory events by long-term therapy. (AU)

• FAPESP's process: 10/12495-6 - Optimization, synthesis and pharmacological evaluation of new drug candidates to treat the symptoms of sickle cell disease
• Grantee: Jean Leandro dos Santos
• Support Opportunities: Regular Research Grants
• FAPESP's process: 09/12664-5 - Pre clinical pharmacokinetics of 1-(2,6-dichlorophenyl)indolin-2-one), a prodrug candidate, with anti-inflammatory properties
• Grantee: Michel Leandro de Campos
• Support Opportunities: Scholarships in Brazil - Master