Balzarini_1999_Mol.Pharmacol_56_1354

Reference

Title : Intracellular metabolism of CycloSaligenyl 3'-azido-2', 3'-dideoxythymidine monophosphate, a prodrug of 3'-azido-2', 3'-dideoxythymidine (zidovudine) - Balzarini_1999_Mol.Pharmacol_56_1354
Author(s) : Balzarini J , Naesens L , Aquaro S , Knispel T , Perno C , De Clercq E , Meier C
Ref : Molecular Pharmacology , 56 :1354 , 1999
Abstract :

The administration of CycloSaligenyl 3'-azido-2',3'-dideoxythymidine monophosphate (CycloSal-AZTMP) to CEM cells resulted in a concentration- and time-dependent conversion to the 5'-monophosphate (AZTMP), 5'-diphosphate (AZTDP), and 5'-triphosphate (AZTTP) derivatives. High ratios of AZTMP/AZTTP were found in the CEM cell cultures treated with CycloSal-AZTMP. The intracellular T(1/2) of AZTTP in CEM cell cultures treated with either AZT and CycloSal-AZTMP was approximately 3 h. A variety of human T- and B-lymphocyte cell lines efficiently converted the prodrug to the AZT metabolites, whereas peripheral blood lymphocytes and primary monocyte/macrophages showed at least 10-fold lower metabolic conversion of the prodrug. CycloSal-AZTMP failed to generate marked levels of AZT metabolites in thymidine kinase-deficient CEM/TK(-) cells, an observation that is in agreement with the substantial loss of antiviral activity of CycloSal-AZTMP in CEM/TK(-) cells. The inability of CycloSal-AZTMP to generate AZTMP in CEM/TK(-) cells is presumably due to a relatively high hydrolysis rate of AZTMP to the parent nucleoside AZT, combined with the inability of CEM/TK(-) cells to phosphorylate AZT to AZTMP through the cytosolic salvage enzyme thymidine kinase.

PubMedSearch : Balzarini_1999_Mol.Pharmacol_56_1354
PubMedID: 10570065

Related information

Citations formats

Balzarini J, Naesens L, Aquaro S, Knispel T, Perno C, De Clercq E, Meier C (1999)
Intracellular metabolism of CycloSaligenyl 3'-azido-2', 3'-dideoxythymidine monophosphate, a prodrug of 3'-azido-2', 3'-dideoxythymidine (zidovudine)
Molecular Pharmacology 56 :1354

Balzarini J, Naesens L, Aquaro S, Knispel T, Perno C, De Clercq E, Meier C (1999)
Molecular Pharmacology 56 :1354