| Literature DB >> 11170035 |
M Shafiee1, S Deferme, A L Villard, D Egron, G Gosselin, J L Imbach, T Lioux, A Pompon, S Varray, A M Aubertin, G Van Den Mooter, R Kinget, C Périgaud, P Augustijns.
Abstract
The in vitro anti-HIV activity, stability, and potential for oral absorption of a phosphotriester derivative of AZT (zidovudine; 3'-azido-2',3'-deoxythymidine) bearing a new esterase-labile S-acyl-2-thioethyl (SATE) group as transient phosphate protection are reported. The biolabile protection is characterized by the presence of a hydroxyl function in the acyl chain. In accordance with previously reported data in the bis(SATE) prodrug series, the present results demonstrate that the studied bis(hydroxytBuSATE)phosphotriester exerts its biological effects via intracellular delivery of the 5'-monophosphate of AZT. The hydroxyl function confers a high resistance against esterase hydrolysis, and the studied prodrug is able to cross the Caco-2 cell monolayers in intact form, suggesting that its further development as a possible anti-HIV pronucleotide candidate is warranted. Copyright 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:448-463, 2001Entities:
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Year: 2001 PMID： 11170035 DOI： 10.1002/1520-6017(200104)90:4<448::aid-jps1003>3.0.co;2-h
Source DB: PubMed Journal: J Pharm Sci ISSN： 0022-3549 Impact factor: 3.534