3,4-Dihydropyrimidine-2(1H)-one/thione Derivatives as Anti-inflammatory and Antioxidant Agents: Synthesis, Biological Activity, and Docking Studies

aims: A series of sixteen new 4-(substituted phenyl) - 6-(substituted phenylamino)-3, 4-dihydropyrimidine-2(1H)-ones/thiones derivatives have been synthesized in two step reaction. background: Free radicals are widely known to play a significant part in the inflammatory process. Many non-steroidal anti-inflammatory medicines have been shown to work as radical scavengers or as inhibitors of free radical generation. Inflammation is a part of the vascular tissues' complicated biological reaction to adverse stimuli like bacteria, damaged cells, or irritants. The organism's protective response to damaging stimuli is inflammation, which aims to get rid of them and start the healing process. The inflammatory response has several advantageous effects, such as stopping the spread of dangerous substances to nearby tissues, getting rid of cell waste and infections, and getting the body ready for repair objective: To synthesize new derivatives as anti-inflammatory and antioxidant agents. method: In first step chalcones (I1-I6) was obtained and in the second step, these chalcones were reacted with urea and thiourea in the presence of potassium hydroxide to obtain the corresponding pyrimidinones and thiopyrimidinones. The structures of the synthesized compounds 4-(substituted phenyl)-6-(substituted phenylamino)-3,4-dihydropyrimidine-2(1H)-ones/thione derivatives are investigated by means of TLC (visualized it in Iodine chamber), IR, mass, 1H-NMR spectral and elemental analysis. The title compounds evaluated for anti-inflammatory as well as antioxidant activity. Anti-inflammatory activity in vivo was carried out by carrageenan induced rat-paw edema method and compared with standard drug diclofenac sodium and antioxidant activity was measured by DPPH, FRAP and Hydrogen peroxide (H2O2) method and compared with standard ascorbic acid. result: Electron donating groups showed better antioxidant activity as compared to electron withdrawing ones in both activities. All the compounds exhibited good to moderate activity. Compound DHPM8 shows better antioxidant activity and compound DHPM6 shows better anti-inflammatory activity while compound DHPM11 shows minimum antioxidant as well as anti-inflammatory activity than other compounds. conclusion: To better understanding, we have performed molecular docking simulation. The molecular docking studies revealed that all synthesized compound were showed good receptor binding interaction in which compound 9 had highest docking score of 9.8 due to interaction with CYS36, PRO153, TYR130, GLY45, LEU152, ARG469, LYS468 and GLU465. other: NA