title: Synthesis, colon-targeted studies and pharmacological evaluation of an anti-ulcerative colitis drug 4-Aminosalicylic acid-β-O-glucoside.
abstract: A glycoside prodrug of 4-aminosalicylic acid (4-ASA) with d-glucose was synthesized for targeted drug delivery to inflammatory bowel. The in vitro assessment of 4-aminosalicylic acid-β-O-glucoside (4-ASA-Glu) as a colon-specific prodrug was studied using colitis rat with the healthy one as control. The stability studies in aqueous buffers (pH 1.2, 6.8 and 7.4) indicated that 4-ASA-Glu was stable over a period of 12 h. The incubation of 4-ASA-Glu with cecal or colonic contents of healthy rats at 37 °C released 4-ASA in 77 or 80% of the dose in 12 h, respectively. The amount of 4-ASA liberated from the incubation of 4-ASA-Glu in cecal or colonic contents of colitis rats at 37 °C was 69 or 79% in 12 h respectively, while less than 9% 4-ASA was detected from the incubation of 4-ASA-Glu with the homogenates of stomach or small intestine. The curative effect of 4-ASA-Glu was evaluated in 2, 4, 6-trinitrobenzenesulfonic acid (TNBS) induced experimental colitis model in male Sprague-Dawley (SD) rats. It was found that 4-ASA-Glu possess significantly ameliorate effect than sulfasalazine, oral 4- and 5-aminosalicylic acid.
authors.affiliation: School of Pharmaceutical Science, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Science, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: Guoli
authors.initials: G
authors.lastname: Wu
authors.affiliation: First Clinical College, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: Huixia
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Institute of Environmental Science, Shanxi University, Taiyuan 030006, China. Electronic address: wangli@sxu.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Science, Shanxi Medical University, Taiyuan 030001, China. Electronic address: zhengbao_z@163.com.
authors.forename: Zhengbao
authors.initials: Z
authors.lastname: Zhao
mesh_terms: D000818:Animals; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000188:drug therapy*; D003106:Colon / Q000187:drug effects* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005960:Glucosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D015394:Molecular Structure; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
chemical_list: C000611513:4-aminosalicylic acid-beta-O-glucoside; D005960:Glucosides; D011355:Prodrugs
keywords: 4-Aminosalicylic acid; 4-Aminosalicylic acid-β-O-glucoside; Glycoside prodrug; Inflammatory bowel disease