arachidonic-acid and Pain

Conjugates of chromone-indole and chromone-pyrazole were screened for cyclooxygenase-2 (COX-2), cyclooxygenase-1 (COX-1) and 5-lipoxygenase (5-LOX) inhibitory activities. Compounds 8 and 9 were identified as preferred inhibitors of COX-2 over the other two enzymes. Their IC50 for COX-2 was 29 nM and 20 nM, respectively and selectivity indices (SI) for COX-2 over COX-1 was 46 and 337. NMR, mass spectral studies and molecular modelling also indicated preferential interactions of compounds 8 and 9 with COX-2. Tested on albino mice against capsaicin induced algesia, compound 8 exhibited analgesic potential comparable to diclofenac. In addition to the biological profile, the desirable physico-chemical properties of these compounds make them promising leads for anti-inflammatory drugs.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Capsaicin; Chromones; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Drug Design; Indoles; Mice; Models, Molecular; Molecular Structure; Pain; Pain Measurement; Pyrazoles; Structure-Activity Relationship

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Atherosclerosis; Fever; Humans; Intramolecular Oxidoreductases; Mice; Mice, Knockout; Microsomes; Pain; Prostaglandin-E Synthases; Stroke