Synthesis and evaluation of analgesic, anti-inflammatory and antioxidant activities of new 6-acyl-3-alkyl-5-methyl-2(3H)-benzoxazolones.
A new series of 6-acyl-3-alkyl-5-methyl-2(3H)-benzoxazolones have been obtained starting from 5-methyl-2(3H)-benzoxazolone. All the compounds have been characterized by IR, 1H-NMR and mass spectroscopy. The new compounds were screened for analgesic and anti-inflammatory activities and ulcerogenic effect. The in vitro antioxidant capacity of the synthesized compounds were tested by the nitric oxide radical scavenging assay. Most of the compounds showed antiinflammatory activity. Among them, 3-[4-(4-fluorophenyl)piperazinomethyl] -6-(3-chlorobenzoyl)-5-methyl-2(3H)-benzoxazolone (3j) was found more potent than the reference drug indometacin (CAS 53-86-1) with 41.66% decrease in edema. Compared with the control, some of the compounds exhibited analgesic effects. Similar to the anti-inflammatory activity results, compound 3j showed the highest analgesic profile with 48.56% inhibition. No active hemorragic focus was observed in the microscopic evaluation in the ulcerogenic effect studies of the tested compounds. 6-(3-Chlorobenzoyl)-5-methyl-2(3H)-benzoxazolone (2b) and 3-[4-(4-fluorophenyl-piperazino)methyl]-6-(3-chlorobenzoyl)-5-methyl-2(3H)-benzoxazolone (3j) showed nearly maximum antioxidant activity compared to ascorbic acid (CAS 50-81-7) with IC50 values of 27.6 and 30.1 microg/mL, respectively.
Koksal
Meric
M
Yeditepe University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Istanbul, Turkey. merickoksal@yeditepe.edu.tr
Kelekci
Nesrin Gokhan
NG
Mercanoglu
Guldem Olguner
GO
Erdogan
Hakki
H
D018712:Analgesics, Non-Narcotic / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use; D001583:Benzoxazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D002351:Carrageenan; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D007202:Indicators and Reagents; D008297:Male; D051379:Mice; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology
D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D001583:Benzoxazoles; D007202:Indicators and Reagents; D002351:Carrageenan