Design, synthesis and molecular docking study of some substituted 4,5- dihydro-2H-indazole derivatives as potential anti-inflammatory agents.
A new series of 4,5-dihydro-2H-indazoles was synthesized and evaluated for anti-inflammatory activity using formalin-induced paw edema and turpentine oil-induced granuloma pouch bioassays. In addition, the inhibitory activity of cyclooxygenase, ulcerogenic effect, and acute toxicity (ALD50) values were also determined. Compounds 10, 13, 15, 16, 18 and 22 were proved to display distinctive anti-inflammatory profiles with a fast onset of action. They revealed super GI safety profile and are well tolerated by the experimental animals with high safety margin (ALD50 >300 mg/Kg). The same active compounds exhibited moderate to powerful selectivity profile towards the inhibition of COX-2 enzyme. Docking poses for the most active compounds separately in the active site of human COX-2 enzyme were also obtained.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, PO Box 80260, Jeddah 21589, Saudi Arabia. badrmona@hotmail.com
Mona H
MH
Badr
Rasha Y
RY
Elbayaa
Ibrahim M
IM
El-Ashmawy
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D005557:Formaldehyde; D006099:Granuloma / Q000139:chemically induced / Q000188:drug therapy*; D006801:Humans; D007191:Indazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008297:Male; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D014425:Turpentine
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D007191:Indazoles; D005557:Formaldehyde; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D014425:Turpentine