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 107
- Downloads 0
Comparative study on the suitability of different substrates for Tannin Acyl Hydrolase production using Aspergillus oryzae
An extracellular tannase produced by the fungus Aspergillus oryzae in solid state fermentation using various agricultural by-products. Among different substrates used the maximum activity of 14.40 U/g/min was...
Nutritional Status and Serum Zinc Levels in HIV Infected Individuals Compared to Control Subjects Undergoing Anti Retro Viral Therapy (ART)
Human immunodeficiency virus (HIV) infected individuals are prone to malnutrition due to increased energy requirements, enteropathy and catabolism. Trace element such as zinc have major role in maintaining a healthy immu...
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...
HPTLC Determination of Amoxicillin Trihydrate and Bromhexine Hydrochloride in Oral Solid Dosage Forms
A simple, accurate, precise and rapid high-performance thin-layer chromatographic method for determination of Amoxicillin Trihydrate and Bromhexine Hydrochloride in Bulk and combined Pharmaceutical Dosage Form was develo...
Studies in Formulation Development of Low Dose Content Drug Using Fluid Bed Granulation Technique
To achieve acceptable content uniformity, a granulation process is generally utilized. Fluid bed granulation, wet granulation, dry granulation was used for granulation purpose for formulation of sustained release tablets...