Synthesis and evaluation of 5-aminosalicyl-glycine as a potential colon-specific prodrug of 5-aminosalicylic acid.
As a new colon-specific prodrug of 5-aminosalicylic acid (5-ASA), 5-aminosalicyl-glycine (5-ASA-Gly) was prepared by a simple synthetic route in good yield. Apparent partition coefficients of 5-ASA-Gly were lower than those of 5-ASA, which determined in CHCl3/pH 6.8 buffer or n-octanol/pH 6.8 buffer system. Stability of 5-ASA-Gly by peptidases was investigated by incubation of 5-ASA-Gly with the homogenates of tissue and contents of stomach, proximal small intestine or distal small intestine of rats at 37 degrees C. 5-ASA was not detected, indicating that the prodrug was stable in the upper intestine. The amount of 5-ASA liberated from incubation of the prodrug in cecal or colonic contents of rats was about 65% or 27% in 8 hrs, respectively, which indicated that the prodrug activation took place more readily in the rat cecum whose bacterial counts are high like human colon. Results from in vitro experiments suggested 5-ASA-Gly as a promising candidate of a colon-specific prodrug of 5-ASA.
Jung
Y J
YJ
College of Pharmacy, Pusan National University, Korea.
Lee
J S
JS
Kim
H H
HH
Kim
Y M
YM
Han
S K
SK
D000636:Aminosalicylic Acids / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D000818:Animals; D002021:Buffers; D002138:Calibration; D002432:Cecum / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003106:Colon / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D006626:Hippurates / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D008297:Male; D019804:Mesalamine / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011355:Prodrugs / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013056:Spectrophotometry, Ultraviolet
C116885:5-aminosalicyl-glycine; D000636:Aminosalicylic Acids; D002021:Buffers; D006626:Hippurates; D011355:Prodrugs; D019804:Mesalamine