title: Synthesis and evaluation of mutual azo prodrug of 5-aminosalicylic acid linked to 2-phenylbenzoxazole-2-yl-5-acetic acid in ulcerative colitis.
abstract: In this study, the syntheses of 4-aminophenylbenzoxazol-2-yl-5-acetic acid, (an analogue of a known nonsteroidal anti-inflammatory drug [NSAID]) and 5-[4-(benzoxazol-2-yl-5-acetic acid)phenylazo]-2-hydroxybenzoic acid (a novel mutual azo prodrug of 5-aminosalicylic acid [5-ASA]) are reported. The structures of the synthesized compounds were confirmed using infrared (IR), hydrogen-1 nuclear magnetic resonance (1H NMR), and mass spectrometry (MS) spectroscopy. Incubation of the azo compound with rat cecal contents demonstrated the susceptibility of the prepared azo prodrug to bacterial azoreductase enzyme. The azo compound and the 4-aminophenylbenzoxazol-2-yl-5-acetic acid were evaluated for inflammatory bowel diseases, in trinitrobenzenesulfonic acid (TNB)-induced colitis in rats. The synthesized diazo compound and the 4-aminophenylbenzoxazol-2-yl-5-acetic acid were found to be as effective as 5-aminosalicylic acid for ulcerative colitis. The results of this work suggest that the 4-aminophenylbenzoxazol-2-yl-5-acetic acid may represent a new lead for treatment of ulcerative colitis.
authors: Department of Medicinal chemistry and Pharmacognosy, Jordan University of Science and Technology, Irbid, Jordan. jilanij@just.edu.jo
authors: Jamal A
authors: JA
authors: Jilani
authors: Maha
authors: M
authors: Shomaf
authors: Karem H
authors: KH
authors: Alzoubi
mesh_terms: D000085:Acetates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001583:Benzoxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D019804:Mesalamine / Q000494:pharmacology*; D011355:Prodrugs; D051381:Rats; D017208:Rats, Wistar; D012459:Salicylates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013055:Spectrophotometry, Infrared; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
chemical_list: C588135:4-aminophenylbenzoxazol-2-yl-5-acetic acid; C588136:5-(4-(benzoxazol-2-yl-5-acetic acid)phenylazo)-2-hydroxybenzoic acid; D000085:Acetates; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001583:Benzoxazoles; D011355:Prodrugs; D012459:Salicylates; D019804:Mesalamine; D014302:Trinitrobenzenesulfonic Acid
keywords: azo prodrug; benzoxazole acetic acid; colon drug delivery
references: Cleve Clin J Med. 1995 Sep-Oct;62(5):317-23
references: 7586488
references: J Rheumatol Suppl. 1980;6:5-11
references: 6771399
references: Drugs. 2008;68(8):1089-103
references: 18484800
references: Prostaglandins Leukot Med. 1983 Apr;10(4):405-9
references: 6407032
references: J Med Chem. 1977 Jun;20(6):797-801
references: 874954
references: Pharmazie. 1998 Aug;53(8):539-43
references: 9741062
references: J Med Chem. 1983 Sep;26(9):1300-7
references: 6136612
references: Gastroenterology. 1989 Mar;96(3):795-803
references: 2914642
references: Curr Drug Deliv. 2012 Mar;9(2):112-21
references: 22283649
references: Cochrane Database Syst Rev. 2011 Jan 19;(1):CD008414
references: 21249709
references: Bioorg Med Chem Lett. 2010 Nov 15;20(22):6538-41
references: 20889341
references: Am J Gastroenterol. 2005 Jun;100(6):1345-53
references: 15929768
references: J Pharm Pharmacol. 1977 Jun;29(6):330-6
references: 18568
references: Br J Dermatol. 1983 Jul;109 Suppl 25:126-9
references: 6305387
references: Gastroenterology. 1989 Jan;96(1):29-36
references: 2535830
references: Skin Pharmacol. 1994;7(6):324-34
references: 7946375
references: Bioorg Med Chem. 2002 Dec;10(12):3997-4004
references: 12413851
references: Gut. 2012 Dec;61(12):1708-15
references: 22187071
references: Gut. 1987 Nov;28(11):1474-7
references: 3428673
references: Scand J Gastroenterol Suppl. 1988;148:7-12
references: 3067340
references: J Med Chem. 1997 Aug 15;40(17):2755-61
references: 9276021
references: Bioorg Med Chem. 2006 Sep 1;14(17):6106-19
references: 16714116
references: Q J Med. 1990 Jun;75(278):551-62
references: 1977185
references: Bioorg Med Chem Lett. 2007 Apr 1;17(7):1897-902
references: 17280832
references: J Enzyme Inhib Med Chem. 2008 Feb;23(1):37-42
references: 18341251
references: Drugs. 1991 Apr;41(4):647-64
references: 1711964
references: J Med Chem. 1975 Nov;18(11):1158-9
references: 1177263
references: Inflamm Bowel Dis. 1997 Summer;3(2):65-78
references: 23282747
references: Gut. 2001 Oct;49(4):552-6
references: 11559654
references: Cancer Lett. 2010 Jan 1;287(1):82-90
references: 19541409
references: J Control Release. 2003 Feb 14;88(1):1-9
references: 12586498