Anti-inflammatory and gastro sparing activity of some new indomethacin derivatives

Indomethacin is a non-steroidal anti-inflammatory drug but its use is associated with high degree of gastric toxicity therefore it is prescribed only in severe conditions. In order to reduce the gastric toxicity of indomethacin, various oxadiazole, triazole, thiadiazole and triazine derivatives have been synthesized. Out of thirteen cyclized derivatives, eleven were screened for anti-inflammatory activity by Winter et al. method. Four compounds showed highly significant activity and were further tested for analgesic, ulcerogenic and lipid peroxidation activities. The tested compounds showed anti-inflammatory activities in the range from about 32% to 85% as compared to that of indomethacin of about 96%. The compounds showing high anti-inflammatory activity also exhibited reduction in severity index. These compounds also produced less malondialdehyde content in gastric mucosa than the standard drug indomethacin. The study showed that the compounds inhibited the induction of gastric mucosal lesions and it can be suggested from our results that their protective effects may be related to inhibition of lipid peroxidation in the gastric mucosa.