Int. J. Mol. Sci. 2012, 13(11), 15305-15320; doi:10.3390/ijms131115305
Article

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

Jean Leandro dos Santos 1,* email, Vanessa Moreira 2 email, Michel Leandro Campos 3 email, Rafael Consolin Chelucci 1 email, Karina Pereira Barbieri 1 email, Pollyana Cristina Maggio de Castro Souto 2 email, Márcio Hideki Matsubara 2 email, Catarina Teixeira 2 email, Priscila Longhin Bosquesi 1 email, Rosângela Gonçalves Peccinini 3 email and Chung Man Chin 1,* email
1 Lapdesf—Laboratory of Research and Drug Development, Drugs and Medicines Department, School of Pharmaceutical Science—UNESP Rodovia Araraquara Jaú Km. 01, 14801-902, Araraquara, SP, Brazil 2 Pharmacology Laboratory, Inflammation unit, Butantan Institute, Vital Brazil Avenue 1500, 05503-900, São Paulo, Brazil 3 Natural Active Principles and Toxicology Department, School of Pharmaceutical Science—UNESP Rodovia Araraquara Jaú Km. 01, 14801-902, Araraquara, SP, Brazil
* Authors to whom correspondence should be addressed.
Received: 17 July 2012; in revised form: 17 October 2012 / Accepted: 15 November 2012 / Published: 19 November 2012
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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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 PGE2 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.
Keywords: NSAIDs; anti-inflammatory; diclofenac; prodrugs; molecular modification; lactam; COX-inhibitor; bioconversion, chronic inflammation

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Cite This Article

MDPI and ACS Style

Santos, J.L.; Moreira, V.; Campos, M.L.; Chelucci, R.C.; Barbieri, K.P.; Souto, P.C.M.C.; Matsubara, M.H.; Teixeira, C.; Bosquesi, P.L.; Peccinini, R.G.; Chin, C.M. Pharmacological Evaluation and Preliminary Pharmacokinetics Studies of a New Diclofenac Prodrug without Gastric Ulceration Effect. Int. J. Mol. Sci. 2012, 13, 15305-15320.

AMA Style

Santos JL, Moreira V, Campos ML, Chelucci RC, Barbieri KP, Souto PCMC, Matsubara MH, Teixeira C, Bosquesi PL, Peccinini RG, Chin CM. Pharmacological Evaluation and Preliminary Pharmacokinetics Studies of a New Diclofenac Prodrug without Gastric Ulceration Effect. International Journal of Molecular Sciences. 2012; 13(11):15305-15320.

Chicago/Turabian Style

Santos, Jean L.; Moreira, Vanessa; Campos, Michel L.; Chelucci, Rafael C.; Barbieri, Karina P.; Souto, Pollyana C.M.C.; Matsubara, Márcio H.; Teixeira, Catarina; Bosquesi, Priscila L.; Peccinini, Rosângela G.; Chin, Chung M. 2012. "Pharmacological Evaluation and Preliminary Pharmacokinetics Studies of a New Diclofenac Prodrug without Gastric Ulceration Effect." Int. J. Mol. Sci. 13, no. 11: 15305-15320.

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