Synthesis of a novel PEGylated colon-specific azo-based 4- aminosalicylic acid prodrug
Objective(s): 4-aminosalicylic acid (4-ASA) is an isomer of mesalazine that has recently been shown to be effective against inflammatory bowel disease (IBD), and more specifically, ulcerative colitis. However, the majority of orally administered 4-ASA is readily and extensively absorbed from the stomach and small intestine, so only a small amount is transported to the colon. A mutual ester and azo prodrug of 4-ASA was synthesized with polyethylene glycol (PEG) and dimethylaniline, respectively , to overcome this issue. Materials and Methods: The 4-ASA prodrug was synthesized via a two-step process and then characterized by 1H-NMR. The stability of the prodrug was evaluated in simulated gastric fluid (pH 1.2). Furthermore, the in vitro release profiles of the drug conjugate was evaluated at pH 1.2, as well as pH 6.8 in the absence or presence of rat cecal content. Results: The prepared prodrug was stable at pH 1.2, indicating that it could be protected from the acidic environment of the stomach. Also, the results of drug release at pH 6.8 showed that the amount of 4-ASA released was 63% within 12 hr in the absence of rat cecal content, while in the presence of rat cecal content, 97% of 4-ASA was released from the prodrug in 6 hr. Conclusion: Overall, the synthesized PEGylated azo-based 4-ASA prodrug could be a potential candidate for targeted drug delivery to the inflamed gut tissue in IBD.
Ester Prodrug of 5-Aminosalicylic Acid for Colon Specific Drug Delivery: Synthesis, Kinetics, Hydrolysis and Stabilities
Acrylic type polymeric systems having degradable ester bonds linked to the 5-aminosalicylic acid (5-ASA), were synthesized and evaluated for colon targeted drug delivery. The obtained prodrug was characterized by FTIR,HNMR,Melting point and Rf value.In vitro drug release study was conducted at pH 1.2,7.4 and in rat fecal matter. Drug release in rat fecal matter at pH 7.4 was found to be most sa...متن کامل
Synthesis and evaluation of a prodrug of 5-aminosalicylic acid for the treatment of ulcerative colitis
Objective(s): This study is aimed to design and synthesize a prodrug of 5-aminosalicylic acid and evaluate its ameliorative effect on experimental ulcerative colitis (UC).Materials and Methods: 5-Aminosalicylic acid-alanine (5-ASA-ALA) was synthesized and characterized. Its stability study was conducted in rat plasma and in the gastroint...متن کامل
Synthesis and characterization of some novel linear azo-azomethine compounds based on 1-bromo, 4-4-4-nitrophenylazo phenoxy butane
The reaction of some carbocyclic and heterocyclic Schiff bases with the synthesized 1-bromo, 4-[4-(4-nitrophenylazo) phenoxy] butane and formation of novel linear azo-azomethine compounds in good to excellent yields were investigated. The compounds were fully characterized by UV-Vis, FT-IR, 1H NMR spectroscopic techniques and elemental analysis. Effects of various solvents on their visible abso...متن کامل
Synthesis and evaluation of mutual azo prodrug of 5-aminosalicylic acid linked to 2-phenylbenzoxazole-2-yl-5-acetic acid in ulcerative colitis
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 magn...متن کامل
5-Aminosalicylic acid (5-ASA) is currently prepared by electrochemical reduction of 5-nitrosalicylic acid (5-NSA) in acidic media. In this work, electrolytic reduction of 5-NSA in alkaline media is presented. Reactionconditions and parameters such as anode and cathode electrodes, electrolyte type, reaction time, temperature,current, and the pH for isolation of product are investigated. The yiel...متن کامل
para-Aminosalicylic acid is a prodrug targeting dihydrofolate reductase in Mycobacterium tuberculosis.
para-Aminosalicylic acid (PAS) is one of the antimycobacterial drugs currently used for multidrug-resistant tuberculosis. Although it has been in clinical use for over 60 years, its mechanism(s) of action remains elusive. Here we report that PAS is a prodrug targeting dihydrofolate reductase (DHFR) through an unusual and novel mechanism of action. We provide evidences that PAS is incorporated i...متن کامل
دوره 23 شماره 6
صفحات 781- 787
تاریخ انتشار 2020-06-01
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