Design ,synthesis and Docking Studies of Novel Diarylpyrazoline and Diarylisoxazoline Derivatives of Expected Anti-inflammatory and Analgesic Activites

Two series of novel non acidic 3, 5-diarylpyrazoline and 3, 5 diarylisoxazoline derivatives were designed to be synthesized and screened for anti-inflammatory and analgesic activities. In addition, molecular modelling and docking of the designed compounds into cyclooxygenase II (COX-II) using Molsoft ICM 3.4-8C program was performed in order to predict the affinity and orientation of the designed compounds at the active site compared with its binding inhibitor celecoxib. The ICM score values show good agreement with predicted binding affinities, where all the designed compounds exhibit ICM score values (range from -88.89 to -70.40) less than celecoxib (-60.71) revealing higher binding affinity with the enzyme. Accordingly, synthesis of the designed compounds via reaction of various propenone derivatives with hydrazine hydrate, phenyl hydrazine or hydroxylamine hydrochlorides were carried out. Evaluation of their activity as anti-inflammatory and analgesics using dextran-induced rat paw edema, formaldehyde arthritis test and paw pressure test, respectively and their ability to induce gastric toxicity was also estimated. All the synthesized compounds exhibited significant activity as anti-inflammatory and analgesic, where compounds 2 and 8 were the most active as anti-inflammatory in dextran-induced rat paw edema, while compounds7 and 10 were the most active as anti-inflammatory in formaldehyde-induced arthritis rat paw edema test. All compounds showed analgesic activity with the most potent compounds were 3, and 10 were the most active. No one of the tested compounds cause gastric toxicity. We can conclude that the synthesized compounds proved a successful hit and seem potentially attractive as anti-inflammatory and analgesic agents.Cairo universit