Design, Synthesis and Antiinflammatory Activity of Novel gamma Tocopherol Naproxen Ester Prodrug.
Journal Title: Journal of Pharmaceutical Sciences and Research - Year 2009, Vol 1, Issue 4
Abstract
Naproxen is widely used for the treatment of arthritic pain. It can induce gastrointestinal (GI) side effects ranging from stomach irritation to ulceration and bleeding. These complications are believed to be determined from the combined effect of the blockage of prostaglandin biosynthesis in the GI tract and direct action of free carboxylic groups. Prodrugs approach have been proposed to overcome the Non-steroidal anti-inflammatory drugs (NSAIDs) side effects by masking the carboxylic acid groups via formation of bioreversible bonds. It has been demonstrated that the production of reactive oxygen species (ROS) plays an important pathogenic role in gastrointestinal ulceration. Our goal was to develop a new Naproxen prodrug which integrates the concepts of prodrug and the beneficial antioxidant effect. For this purpose we designed and synthesized naproxen esters containing tocopherols. Among the possible antioxidant compounds we focused our attention on gamma-tocopherol for its potent antioxidant properties and anti-inflammatory activity. In addition, esterification of phenolic group on chroman ring of tocopherols, to form the prodrug, is expected to increase the stability to oxidation of the vitamin. In the present paper, we report the synthesis and the in vitro enzymatic and non-enzymatic hydrolysis of two prodrug esters of naproxen with alpha- and gamma-tocopherols. We also investigated the oral pharmacokinetic in rabbit and probed the preliminary pharmacological evaluation in rat. The synthesized prodrugs exhibited antiinflammatory activity with a strong and significant reduction in gastrolesivity.
Authors and Affiliations
Angelo Spadaro , Claudio Bucolo , Giuseppe Ronsisvalle , Maria Pappalardo
Keywords
Related Articles
- EP ID EP134203
- DOI -
- Views 112
- Downloads 0
Phyto-pharmacological and plant tissue culture overview of Tylophora indica (burm f.) Merill.
Tylophora indica is a climbing perennial plant indigenous to India, where it is grows wild in the southern and eastern region and has long-standing reputation as a remedy for asthma (hence the Tylophora asthmatica). The...
Moringa oleifera: a natural gift-A review
Moringa oleifera, Lam {Syn M.pterygosperma Gaertn} usually mentioned in literature as Moringa, is a natural as well as cultivated variety of the genus Moringa belonging to family Moringaceae .It is one of the riches...
Development and validation of RP-HPLC method for the estimation of nevirapine in bulk drug and tablets
A reverse phase high performance liquid chromatography [RP-HPLC] method has been developed for the estimation of Nevirapine in bulk drug and pharmaceutical dosage forms. The quantification was carried out on Octa Decyl S...
Intellectual Property RLghts
Antibacterial and Antifungal Studies of Mirabilus jalap Leaf Extracts.
Five different crude extracts: petroleum ether, chloroform, ethyl ether, ethanol and aqueous extract of Mirabilus jalap have been studied for both in vitro antibacterial and antifungal activites. The different...