Preparation and Synthetic Application of Naproxen-Containing Diaryliodonium Salts

The synthesis of naproxen-containing diaryliodonium salts has been realized from naproxen methyl ester and ArI(OH)OTs activated by trimethylsilyl trifluoromethanesulfonate (TMSOTf) in a solvent mixture comprising dichloromethane and 2,2,2-trifluoroethanol (TFE). Those iodonium salts have been successfully used in the functionalization of an aromatic ring of naproxen methyl ester, including fluorination, iodination, alkynylation, arylation, thiophenolation, and amination and esterification reactions. Moreover, further hydrolysis of the obtained 5-iodo-naproxen methyl ester afforded 5-iodo-naproxen.

Comparison between Lipase Performance Distributed at the O/W Interface by Membrane Emulsification and by Mechanical Stirring

Multiphase bioreactors using interfacial biocatalysts are unique tools in life sciences such as pharmaceutical and biotechnology. In such systems, the formation of microdroplets promotes the mass transfer of reagents between two different phases, and the reaction occurs at the liquid–liquid interface. Membrane emulsification is a technique with unique properties in terms of precise manufacturing of emulsion droplets in mild operative conditions suitable to preserve the stability of bioactive labile components. In the present work, membrane emulsification technology was used for the production of a microstructured emulsion bioreactor using lipase as a catalyst and as a surfactant at the same time. An emulsion bioreaction system was also prepared by the stirring method. The kinetic resolution of (S,R)-naproxen methyl ester catalyzed by the lipase from Candida rugosa to obtain (S)-naproxen acid was used as a model reaction. The catalytic performance of the enzyme in the emulsion systems formulated with the two methods was evaluated in a stirred tank reactor and compared. Lipase showed maximum enantioselectivity (100%) and conversion in the hydrolysis of (S)-naproxen methyl ester when the membrane emulsification technique was used for biocatalytic microdroplets production. Moreover, the controlled formulation of uniform and stable droplets permitted the evaluation of lipase amount distributed at the interface and therefore the evaluation of enzyme specific activity as well as the estimation of the hydrodynamic radius of the enzyme at the oil/water (o/w) interface in its maximum enantioselectivity.

Gastroentero-histopathology Studies of Synthesized Naproxen Esters in Young Healthy Sprague-Dawley Rat Model

Naproxen and its synthesized esters namely naproxen methyl ester, C15H16O3 (compound 1), ethyl ester, C16H17O3 (compound 2) and isopropyl ester, C17H20O3 (compound 3) were subjected to NSAID induced gastro-ulcergenecity studies on young, healthy male rat model. Rats (Rattus novergicus: Sprague-Dawley strain) of 2-months old weighing 95–105 g were administered with naproxen (10 mg/kg b.w.) compound 1 (10.609 mg/kg b.w.), compound 2 (11.217 mg/kg b.w.) and compound 3 (11.826 mg/kg b.w.) twice daily for 4.5 days. The naproxen esters appeared to induce significantly less GI injury and bleeding both in microscopic and macroscopic examinations. This study can be a basis of reference for further acute, chronic or subchronic toxicity studies in various in-vivo models.Dhaka Univ. J. Pharm. Sci. 14(1): 49-53, 2015 (June)

Enhanced catalysis and enantioselective resolution of racemic naproxen methyl ester by lipase encapsulated within iron oxide nanoparticles coated with calix[8]arene valeric acid complexes

In this study, two types of nanoparticles have been used as additives for the encapsulation of Candida rugosa lipase via the sol–gel method.