Pharmacological Evaluation and Preliminary Pharmacokinetics Studies of a New Diclofenac Prodrug without Gastric Ulceration Effect
by
Jean Leandro dos Santos 1,*, Vanessa Moreira 2, Michel Leandro Campos 3, Rafael Consolin Chelucci 1, Karina Pereira Barbieri 1, Pollyana Cristina Maggio de Castro Souto 2, Márcio Hideki Matsubara 2, Catarina Teixeira 2, Priscila Longhin Bosquesi 1, Rosângela Gonçalves Peccinini 3 and Chung Man Chin 1,*
Jean Leandro dos Santos 1,*, Vanessa Moreira 2, Michel Leandro Campos 3, Rafael Consolin Chelucci 1, Karina Pereira Barbieri 1, Pollyana Cristina Maggio de Castro Souto 2, Márcio Hideki Matsubara 2, Catarina Teixeira 2, Priscila Longhin Bosquesi 1, Rosângela Gonçalves Peccinini 3 and Chung Man Chin 1,*
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.
Int. J. Mol. Sci. 2012, 13(11), 15305-15320; https://doi.org/10.3390/ijms131115305
Received: 17 July 2012 / Revised: 17 October 2012 / Accepted: 15 November 2012 / Published: 19 November 2012
(This article belongs to the Section Biochemistry)
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.
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Keywords:
NSAIDs; anti-inflammatory; diclofenac; prodrugs; molecular modification; lactam; COX-inhibitor; bioconversion, chronic inflammation
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This is an open access article distributed under the Creative Commons Attribution License
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.
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