Thiazolamide–Ascorbic Acid Conjugate: a γ-Secretase Inhibitor with Enhanced Blood–Brain Barrier Permeation

Younes Laras; Mahmoud Sheha; Nicolas Pietrancosta; Jean-Louis Kraus

doi:10.1071/CH06441

RESEARCH ARTICLE

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Thiazolamide–Ascorbic Acid Conjugate: a γ-Secretase Inhibitor with Enhanced Blood–Brain Barrier Permeation

Younes Laras ^A , Mahmoud Sheha ^B , Nicolas Pietrancosta ^A and Jean-Louis Kraus ^A ^C

+ Author Affiliations

- Author Affiliations

^A Laboratoire de Chimie Biomoléculaire. UMR-CNRS 6216, IBDML, Université de la Méditerranée, 13288 Marseille cedex 9, France.

^B Medicinal Pharmaceutical Chemistry Department, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.

^C Corresponding author. Email: kraus@luminy.univ-mrs.fr

Australian Journal of Chemistry 60(2) 128-132 https://doi.org/10.1071/CH06441
Submitted: 22 November 2006 Accepted: 13 December 2006 Published: 13 February 2007

Abstract

One of the major problems of the current therapy of brain diseases such as Alzheimer’s disease is the distribution of drugs to the central nervous system (CNS). Difficulties in traversing the blood–brain barrier (BBB) often impair the efficacy of valuable drugs. Using the ascorbic acid–drug conjugate concept, we have succeeded in developing a thiazolamide conjugate that shows an improved pharmacokinetic profile compared to the parent thiazolamide previously reported.

Acknowledgments

INSERM (Institut National de la Santé et de la Recherche Médicale) is greatly acknowledged for financial support. We are grateful to K. Dudley (Université de la Méditerranée, IBDML, for the preparation of the manuscript. We are indebted to Michael S. Wolfe and Frédéric Bihel (Harvard Medical School) for performing the γ-secretase assays.

References

Thiazolamide–Ascorbic Acid Conjugate: a γ-Secretase Inhibitor with Enhanced Blood–Brain Barrier Permeation

Abstract

Acknowledgments

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