DDC- and 3TC-bis(SATE) Monophosphate Prodrugs Overcome Cellular Resistance Mechanisms to HIV-1 Associated with Cytidine Kinase Deficiency

1 April 1999

journal article
research article
Published by Taylor & Francis in Nucleosides and Nucleotides

Vol. 18 (4-5) , 921-926
https://doi.org/10.1080/15257779908041600

Abstract

A 2,3′-dideoxycytidine (ddC)-resistant T-lymphoid cell line (MOLT-4/8^rddC²⁵⁰), in which deoxycytidine kinase (dCK) gene-expression was decreased when compared with parental cells, has been selected. Cytotoxic and antiretroviral activity of ddC and 3TC was significantly lower in MOLT-4/8^rddC²⁵⁰ than in parental MOLT-4/8 cells. ddC- and 3TC-bis(SATE)phosphotriesters completely overcame cellular resistance mechanisms and showed comparable both cytotoxic and antiretroviral activity in parental and ddC-resistant cells.

Keywords

This publication has 9 references indexed in Scilit:

Rational design for cytosolic delivery of nucleoside monphosphates : “SATE” and “DTE” as enzyme-labile transient phosphate protecting groups
Published by Elsevier ,2001
Human Immunodeficiency Virus Resistance to AZT in MOLT4/8 Cells is Associated with a Lack of AZT Phosphorylation and is Bypassed by AZT-Monophosphate SATE Prodrugs
Antiviral Chemistry and Chemotherapy, 1997
The Inhibitory Effect of ddC on Human Immunodeficiency Virus Replication Diminishes in Cells that are Chronically Exposed to the Drug
Antiviral Chemistry and Chemotherapy, 1997
Antiretroviral drugs for AIDS
The Lancet, 1996
2′,3′-Dideoxycytidine metabolism in a new drug-resistant cell line
Biochemical Journal, 1995
Mononucleoside Phosphotriester Derivatives with S-Acyl-2-thioethyl Bioreversible Phosphate-Protecting Groups: Intracellular Delivery of 3'-Azido-2',3'-dideoxythymidine 5'-Monophosphate
Journal of Medicinal Chemistry, 1995
Phosphorylation of 3'-azido-3'-deoxythymidine and selective interaction of the 5'-triphosphate with human immunodeficiency virus reverse transcriptase.
Proceedings of the National Academy of Sciences, 1986
Inhibition of the in vitro infectivity and cytopathic effect of human T-lymphotrophic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) by 2',3'-dideoxynucleosides.
Proceedings of the National Academy of Sciences, 1986
Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays
Journal of Immunological Methods, 1983