Pharmacological activity and hydrolysis behavior of novel ibuprofen glucopyranoside conjugates

Novel ester prodrugs (II, III and IV) of ibuprofen (I) were synthesized using α-methyl, ethyl and propyl glucopyranoside as promoieties and tested for their anti-inflammatory, analgesic and ulcerogenic activities. Study of their chemical hydrolysis in aqueous buffer (pH 3.0–10.0) showed that these compounds acted as true prodrugs of ibuprofen, giving the ibuprofen and alkyl glucopyranoside. Additionally, all the derivatives studied did cleave rapidly inside the biological system and on oral administration did elicit a pharmacological profile quite similar to that of ibuprofen, but, unlike this drug, they displayed reduced gastric ulceration. In conclusion, these alkyl glucopyranoside esters have promising properties as prodrugs for oral delivery of ibuprofen.

Graphical abstractNovel ibuprofen ester prodrugs (II, III, and IV) were synthesized by directly coupling ibuprofen with α-methyl, ethyl and propyl glucopyranoside using immobilized lipase as biocatalyst in acetonitrile. Preliminary biological and pharmacological evaluation of glucopyranoside esters of ibuprofen indicates that esterification of free carboxylic group in ibuprofen remarkably suppresses its gastric ulceration without affecting its anti-inflammatory and analgesic activity.Figure optionsDownload full-size imageDownload as PowerPoint slide