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Structural Analysis of 5-aminosalicyl-L-glutamic Acid, a Colon-specific Prodrug of 5-aminosalicylic Acid, for Colon-specific Deconjugation

  • Received : 2010.06.09
  • Accepted : 2010.07.27
  • Published : 2010.08.20

Abstract

In a previous paper, we showed that 5-aminosalicyl-L-aspartic acid (5-ASA-Asp) has much greater deconjugation efficiency in the cecal contents than does 5-aminosalicyl-L-glutamic acid (5-ASA-Glu). To explore a reason for ineffective deconjugation of 5-ASA-Glu, structural analysis of the conjugate was performed. Aromatic acyl-L-glutamic acid derivatives, N-benzoyl-glumatic acid (BA-Glu), N-(2-hydroxybenzoyl)-glutamic acid (SA-Glu), N-(3-aminobenzoyl)-glutamic acid (3-ABA-Glu) and N-(4-aminobenzoyl)-glutamic acid (4-ABA-Glu), were prepared and incubated in the cecal contents. The deconjugation rates were compared with that of 5-ASA-Glu. The order of the rates was BA-Glu $\approx$ 4-ABA-Glu $\approx$ 3-ABA-Glu $\gg$ SA-Glu $\approx$ 5-ASA-Glu. The deconjugation of the aromatic acyl-L-glutamic acid derivatives was carried out by enzyme(s) in the cecal contents since the deconjugation did not occur in the autoclaved cecal contents and on incubation with N-benzoyl-D-glutamic acid. Our data suggest that the 2-hydroxyl group in 5-ASA is ascribed to the poor deconjugation of 5-ASA-Glu in the cecal contents.

Keywords

References

  1. Chourasia, M.K., Jain, S.K., 2003. Pharmaceutical approaches to colon targeted drug delivery systems, J Pharm Pharmaceut Sci. 6(1), 33-66.
  2. Crotty, B., Jewell, D.P., 1992. Drug therapy of ulcerative colitis, Br J Clin Pharmacol. 34(3), 189-198. https://doi.org/10.1111/j.1365-2125.1992.tb04124.x
  3. Jung, Y.J., Lee, J.S., Kim, Y.M., 2001. Colon-specific prodrugs of 5-aminosalicylic acid: synthesis and in vitro/in vivo properties of acidic amino acid derivatives of 5-aminosalicylic acid, J Pharm Sci. 90(11), 1767-1775. https://doi.org/10.1002/jps.1126
  4. Jung, Y.J., Lee, J.S., Kim, Y.M., 2000. Synthesis and in vitro/in vivo evaluation of 5-aminosalicyl-glycine as a colon-specific prodrug of 5-aminosalicylic acid, J Pharm Sci. 89(5), 594-602. https://doi.org/10.1002/(SICI)1520-6017(200005)89:5<594::AID-JPS5>3.0.CO;2-8
  5. Kim, H., Kong, H., Choi, B., Yang, Y., Kim, Y., Lim, M.J., Neckers, L., Jung, Y., 2005. Metabolic and pharmacological properties of rutin, a dietary quercetin glycoside, for treatment of inflammatory bowel disease, Pharm Res. 22(9), 1499-1509. https://doi.org/10.1007/s11095-005-6250-z
  6. Lofberg, R., 2003. Review article: medical treatment of mild to moderately active Crohn's disease, Aliment Pharmacol Ther. 17 Suppl 2 18-22.
  7. Novis, B.H., Korzets, Z., Chen, P., Bernheim, J., 1988. Nephrotic syndrome after treatment with 5-aminosalicylic acid, Br Med J (Clin Res Ed). 296(6634), 1442.
  8. Sinha, V.R., Kumria, R., 2001. Polysaccharides in colon-specific drug delivery, Int J Pharm. 224(1-2), 19-38. https://doi.org/10.1016/S0378-5173(01)00720-7
  9. Sinha, V.R., Kumria, R., 2001. Colonic drug delivery: prodrug approach, Pharm Res. 18(5), 557-564. https://doi.org/10.1023/A:1011033121528
  10. Sinha, V.R., Kumria, R., 2003. Microbially triggered drug delivery to the colon, Eur J Pharm Sci. 18(1), 3-18. https://doi.org/10.1016/S0928-0987(02)00221-X
  11. Van den Mooter, G., 2006. Colon drug delivery, Expert Opin Drug Deliv. 3(1), 111-125. https://doi.org/10.1517/17425247.3.1.111