Synthesis, characterization and evaluation of analgesic and anti-inflammatory activities of some novel indoles

Abstract

Purpose: Long-term clinical usage of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with significant side effects - gastrointestinal lesions, bleeding and nephrotoxicity. Therefore, the discovery of new safer antiinflammatory drugs represents a challenging goal for this research area. Methods: Various derivatives of 3-(2-aminopyrimidin-4-yl) indoles viz. 4-(4-substitutedphenyl)-6-(2-(4- substitutedphenyl)-1H-indol-3-yl) pyrimidin-2-amine (4a-4r) were synthesized by cyclization of (3-(4- substitutedphenyl)-1-(2-(4-substitutedphenyl)-1H-indol-3-yl) prop-2-en-1-one) of indole with guanidine hydrochloride in the presence of sodium isopropoxide. Their structures were confirmed by FTIR, 1H NMR and elemental analysis. These compounds were investigated for their analgesic, inflammatory and ulcerogenic activities. Results: All the compounds tested (4a-4r) showed analgesic and inflammatory activities. Seven compounds (4d, e, h, j, k, q, p) out of 18 compounds showed antiinflammatory activity comparable to that of the reference standard, indomethacin, but with much lower ulcerogenic action. Compounds 4j and 4k showed 87.4 and 88.2 % inhibition of paw edema, 78.5 and 76.6 % protection against acetic acid-induced writhings and 0.89 and 1.12 of severity index, respectively, compared to 92.7 %, 82.8 % and 2.2, respectively, for indomethacin. Conclusion: The results show that incorporation of an appropriately substituted pyrimidine ring in indole nucleus can afford molecules with good analgesic and anti-inflammatory activities but with reduced gastric irritation. © Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City.