Inflammation is a common immune response to harmful pathogens or damaged cells. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat inflammation and pain. These drugs can also be used to treat inflammation due to diseases such as cancer, rheumatoid arthritis, and Alzheimer’s disease. NSAIDs treat this inflammation by inhibiting the cyclooxygenase-2 (COX-2) enzyme system, which predominates at sites of inflammation as it releases prostaglandins that result in vasodilation. However, there are drawbacks to the current NSAIDs being used, as they do not selectively inhibit the COX-2 enzyme. A current aim in the development of NSAIDs is to have them selectively inhibit the COX-2 enzyme, as the inhibition of the COX-1 enzyme results in adverse side effects, such as gastric lesions and perforation. The current drug design process has focused on modifying existing NSAIDs, such as ibuprofen, in such a way that they retain their anti-inflammatory properties while decreasing the adverse side effects. In the present study, a new set of hybrid conjugates synthesized by molecular hybridization approach to overcome the drawbacks of the current non-steroidal anti-inflammatory drugs. Synthesized conjugates were screened for their anti-inflammatory, analgesic, and ulcerogenic properties. Few conjugates were found to have significant anti-inflammatory properties in the carrageenan-induced rat paw edema test, while a fair number of conjugates showed promising peripheral analgesic activity in the acetic acid-induced writhing test as well as central analgesic properties in the <i>in vivo </i>hot plate technique. The newly synthesized conjugates did not display any ulcerogenic liability. <i>In vitro</i>, COX-1, and COX-2 enzyme inhibition studies revealed some compounds are more selective toward COX-2 compared with reference drugs.

Molecular hybridization of NSAIDs: Synthesis, computational studies, and evaluation of anti-inflammatory and analgesic properties

ACS Fall 2021

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