![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
J Balzarini, H Egberink, K Hartmann, D Cahard, T Vahlenkamp, H Thormar, E De Clercq and C McGuigan
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium. jan.balzarini@rega.kuleuven.ac.be
2',3'-Didehydro-2',3'-dideoxythymidine (d4T) and its lipophilic 5'- monophosphate triester prodrug, So324, were evaluated for their antiretroviral and metabolic properties in four different animal species cell lines. The antiretrovirus activity of So324 was approximately 4-10-fold greater than that of d4T against human immunodeficiency virus types 1 and 2 and simian immunodeficiency virus in human T lymphocyte CEM and MT-4 cells and against feline immunodeficiency virus in feline Crandell kidney cells, 50-fold greater against visna virus in sheep choroid plexus cells, but 5-fold inferior against murine (Moloney) sarcoma virus in murine embryo fibroblast (C3H) cells. Although the administration of both d4T and So324 resulted in the formation of the 5'-monophosphate (d4T-MP), 5'-diphosphate, and 5'-triphosphate in the different cell lines, a new d4T metabolite markedly accumulated in So324-treated cells and exceeded d4T-TP levels by 13-242-fold depending on the cell line used. This metabolite could be identified as alaninyl d4T-MP. Alanyl d4T-MP may be considered to be an intracellular depot form of d4T and/or d4T-MP, which may account for the superior antiretroviral activity of the lipophilic d4T-MP triester So324 compared with d4T.
This article has been cited by other articles:
|
|
 |
|
  O. J. D'Cruz, P. Samuel, B. Waurzyniak, and F. M. Uckun Development and Evaluation of a Thermoreversible Ovule Formulation of Stampidine, a Novel Nonspermicidal Broad-Spectrum Anti-Human Immunodeficiency Virus Microbicide Biol Reprod, December 1, 2003; 69(6): 1843 - 1851. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Reid, P. Wielinga, N. Zelcer, M. de Haas, L. van Deemter, J. Wijnholds, J. Balzarini, and P. Borst Characterization of the Transport of Nucleoside Analog Drugs by the Human Multidrug Resistance Proteins MRP4 and MRP5 Mol. Pharmacol., May 1, 2003; 63(5): 1094 - 1103. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. M. Uckun, C.-L. Chen, P. Samuel, S. Pendergrass, T. K. Venkatachalam, B. Waurzyniak, and S. Qazi In Vivo Antiretroviral Activity of Stampidine in Chronically Feline Immunodeficiency Virus-Infected Cats Antimicrob. Agents Chemother., April 1, 2003; 47(4): 1233 - 1240. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-L. Chen, G. Yu, T. K. Venkatachalam, and F. M. Uckun Metabolism of Stavudine-5'-[p-Bromophenyl Methoxyalaninyl Phosphate], Stampidine, in Mice, Dogs, and Cats Drug Metab. Dispos., December 1, 2002; 30(12): 1523 - 1531. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. M. Uckun, S. Pendergrass, T. K. Venkatachalam, S. Qazi, and D. Richman Stampidine Is a Potent Inhibitor of Zidovudine- and Nucleoside Analog Reverse Transcriptase Inhibitor-Resistant Primary Clinical Human Immunodeficiency Virus Type 1 Isolates with Thymidine Analog Mutations Antimicrob. Agents Chemother., November 1, 2002; 46(11): 3613 - 3616. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-L. Chen, T. K. Venkatachalam, Z.-H. Zhu, and F. M. Uckun In Vivo Pharmacokinetics and Metabolism of Anti-Human Immunodeficiency Virus Agent d4T-5'-[p-Bromophenyl Methoxyalaninyl Phosphate] (SAMPIDINE) in Mice Drug Metab. Dispos., July 1, 2001; 29(7): 1035 - 1041. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Schneider, R. Biondi, R. Sarfati, F. Agou, C. Guerreiro, D. Deville-Bonne, and M. Veron The Mechanism of Phosphorylation of Anti-HIV D4T by Nucleoside Diphosphate Kinase Mol. Pharmacol., May 1, 2000; 57(5): 948 - 953. [Abstract] [Full Text]
|
|
|
|
|
|
D. Saboulard, L. Naesens, D. Cahard, A. Salgado, R. Pathirana, S. Velazquez, C. McGuigan, E. De Clercq, and J. Balzarini Characterization of the Activation Pathway of Phosphoramidate Triester Prodrugs of Stavudine and Zidovudine Mol. Pharmacol., October 1, 1999; 56(4): 693 - 704. [Abstract] [Full Text]
|
|
 |
 |
 |
|
 |
 |
 |
