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.

Gut microbiota mediates the absorption of FLZ, a new drug for Parkinson's disease treatment

“…It was reported that more than 30 commonly prescribed drugs were metabolically altered by the enzymes in gut microbiota 24 , 25 , 26 , including methylase/demethylase, β -glucuronidase, nitroreductase, azoreductase, and so on 27 , 28 , 29 , 30 , 31 . For example, sulfasalazine, a sulfa drug used for the treatment of ulcerative colitis, is absorbed in the colon and converted to its pharmacologically active form of 5-amino 5-salicylic acid by azoreductase in gut microbiota 32 , 33 . FLZ is a novel synthetic derivative of squamosamide for the treatment of PD.…”

Synthesis, Characterization and Biological Evaluation of Some 2-Arylbenzoxazole Acetic Acid Derivatives as Promising Anticancer Agents

“…Oxidative coupling of benzaldehyde with o-aminophenol utilizing lead tetraacetate represents one of these synthetic methods. Although it is not among the popular OD Sample Percentage of Cell Viability = ññññññññññññ × 100 1OD Control methods, possibly due to the oxidative power of lead tetraacetate (14,15). It is reported that lead tetraacetate can cause oxidative decarboxylation of organic carboxylic compounds (16).…”

Inflammation-Responsive Polymers

“…The urea linkages are cleaved by ureases generated by bacteria delivering the antibiotic, enhancing the efficacy and minimizing side effects (Xu et al, 2013). Another bacteria-generated enzyme that may be used with this purpose is the azoreductase, but, to date, the introduction of azo moieties has only been employed in the design of prodrugs (Jilani et al, 2013) and on a dual responsive system that will be described later.…”