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

International Journal of Molecular Sciences

Jean Leandro dos Santos³  Vanessa Moreira¹  Michel Leandro Campos²  Rafael Consolin Chelucci³  Karina Pereira Barbieri³  Pollyana Cristina Maggio de Castro Souto¹  Márcio Hideki Matsubara¹  Catarina Teixeira¹  Priscila Longhin Bosquesi³  Rosângela Gon๺lves Peccinini² 

[1] Pharmacology Laboratory, Inflammation unit, Butantan Institute, Vital Brazil Avenue 1500, 05503-900, São Paulo, Brazil; E-Mails:;Natural Active Principles and Toxicology Department, School of Pharmaceutical Science—UNESP Rodovia Araraquara Jaú Km. 01, 14801-902, Araraquara, SP, Brazil; E-Mails:;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; E-Mails:

关键词: NSAIDs;    anti-inflammatory;    diclofenac;    prodrugs;    molecular modification;    lactam;    COX-inhibitor;    bioconversion;    chronic inflammation;   

DOI  :  10.3390/ijms131115305

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.