The Study Of The Anti-Inflammatory Potency Of Novel Spirooxindole Compound

Inflammation is a complex host’s normal defense reaction to pathogenic factors. The manifestation of inflammation is redness, swelling, heat, pain and functional disorder. Previous evidence has suggested that inflammation cause a heavy burden for the public health. Remarkably, anti-inflammatory drugs have now become the second largest category of drugs after the anti-infective drugs in clinical treatment. Currently, the most widely used anti-inflammatory drugs in the clinical treatment is non-steroidal anti-inflammatory drugs (NSAIDs) and epinephrine corticosteroids. However, the clinical application of above drugs is limited by their various side effects. Thus, the development of novel anti-inflammatory therapeutics is of great importance.NSAIDs inhibit the synthesis of prostaglandins (PGs) through the suppression of cyclooxygenase (COX), and thus to exert the anti-inflammatory potency. However, the application of NSAIDs is limited by its side effects such as gastrointestinal damage. In the present study, we report a novel spirooxindole compound Q34, which possesses good anti-inflammatory activity with low gastrointestinal injury. Our data show that Q34 also has good analgesic activity. Mechanistic study demonstrates that Q34 presents a new kind of COX inhibitors with novel structure. At the mediator level, Q34 decreased the production of NO. At the signal level, Q34 inhibited the activation of MAPK/ERK and NF-κB signal pathways. In addition, we also found that Q34 exhibit the anti-inflammatory activity via the nitric oxide synthase system, indicating that the nitric oxide synthase would be a potential target for Q34. Taken together, our findings provide new compound lead for the development of anti-inflammatory drug and new clue for the mechanistic study of COX inhibitors.