Dhaneshwar Suneela S, Gairola Neha, Kandpal Mini, Vadnerkar Gaurav, Bhatt Lokesh
Department of Pharmaceutical Chemistry, Bharati Vidyapeeth University, Poona College of Pharmacy, Pune 411038, Maharashtra, India.
Bioorg Med Chem. 2007 Jul 15;15(14):4903-9. doi: 10.1016/j.bmc.2007.04.045. Epub 2007 Apr 29.
Mutual azo prodrug of 5-aminosalicylic acid with l-tryptophan was synthesized by coupling l-tryptophan with salicylic acid, for targeted drug delivery to the inflamed gut tissue in inflammatory bowel disease. The structure of synthesized prodrug was confirmed by elemental analysis, IR and NMR spectroscopy. In vitro kinetic studies in HCl buffer (pH 1.2) showed negligible release of 5-aminosalicylic acid, whereas in phosphate buffer (pH 7.4) 18% release was observed over a period of 7 h. In rat fecal matter, 87.9% of 5-aminosalicylic acid was released with a half-life of 143.6 min, following first order kinetics. The azo conjugate was evaluated for its ulcerogenic potential by Rainsford's cold stress method. The ameliorating effect of the azo conjugate and therapeutic efficacy of the carrier system was evaluated in trinitrobenzenesulfonic acid-induced experimental colitis model. The synthesized prodrug was found to be equally effective in mitigating the colitis in rats as that of sulfasalazine without the ulcerogenicity of 5-aminosalicylic acid.
通过将L-色氨酸与水杨酸偶联，合成了5-氨基水杨酸与L-色氨酸的相互偶氮前药，用于在炎症性肠病中靶向药物递送至炎症性肠道组织。通过元素分析、红外光谱和核磁共振光谱确认了合成前药的结构。在HCl缓冲液（pH 1.2）中的体外动力学研究表明，5-氨基水杨酸的释放可忽略不计，而在磷酸盐缓冲液（pH 7.4）中，在7小时内观察到18%的释放。在大鼠粪便中，5-氨基水杨酸的87.9%以一级动力学释放，半衰期为143.6分钟。通过Rainsford冷应激法评估偶氮缀合物的致溃疡潜力。在三硝基苯磺酸诱导的实验性结肠炎模型中评估了偶氮缀合物的改善作用和载体系统的治疗效果。发现合成的前药在减轻大鼠结肠炎方面与柳氮磺胺吡啶同样有效，且无5-氨基水杨酸的致溃疡性。
