Antioxidant Activity and Inhibition of Human Neutrophil Oxidative Burst Mediated by Arylpropionic Acid Non-steroidal Anti-inflammatory Drugs(Medicinal Chemistry)

It has been suggested that the anti-inflammatory activity of some non-steroidal anti-inflammatory drugs (NSAIDs) may be partly due to their ability to scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS), as well as to inhibit the respiratory burst of neutrophils triggered by various activating agents. Therefore, the aim of the present work was to evaluate and compare the potential scavenging activity for an array of ROS (O^<・->_2, H_2O_2, HO^・, ROO^・ and HOCl) and RNS (^・NO and ONOO^-) using in vitro non-cellular screening systems as well as a cellular screening system (human neutrophil oxidative burst), mediated by the arylpropionic acid derivatives (APAs) NSAIDs ibuprofen, flurbiprofen, fenoprofen, fenbufen, ketoprofen, naproxen and indoprofen. The results obtained in the present work demonstrate that under the present experimental conditions, many of the studied APA NSAIDs showed O^<・->_2 scavenging activity (fenbufen≈flurbiprofen≈indoprofen≈ketoprofen), H_2O_2 (ketoprofen≈indoprofen≈fenbufen>flurbiprofen>naproxen), HO^・(fenoprofen≈ibuprofen>fenbufen≈flurbiprofen>ketoprofen>indoprofen≈naproxen), ^・NO (indoprofen>naproxen), ONOO^- (indoprofen>naproxen>fenoprofen≈flurbiprofen≈ibuprofen), as well as inhibit myeloperoxidase (MPO) activity (indoprofen) and scavenge human neutrophil derived ROS (ketoprofen>indoprofen>fenbufen>flurbiprofen). The observed effects, if confirmed in vivo, may strongly contribute to the anti-inflammatory therapeutical activity observed with these NSAIDs.