STUDIES ON THE METABOLISM OF 2,5'-ANHYDRO-3'-AZIDO-3'-DEOXYTHYMIDINE (MEETING ABSTRACT) NLM AIDSLINE Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.

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STUDIES ON THE METABOLISM OF 2,5'-ANHYDRO-3'-AZIDO-3'-DEOXYTHYMIDINE (MEETING ABSTRACT)

Proc Annu Meet Am Assoc Cancer Res; 33:A119 1992. Unique Identifier : AIDSLINE ICDB/92682653
Sun AS; Prusoff WH; Dept. of Pharmacology, Yale Univ. Sch. of Medicine, New Haven, CT; 06510

Abstract: 2,5'-Anhydro-3'-azido-3'-deoxythymidine (anAZT) has been reported to have antiviral activity against HIV-1 in cell culture but is about 4- to 5-fold less inhibitory than AZT. Under investigation is whether the antiviral activity of anAZT is a property of the molecule per se, or whether it is converted to AZT by a cleavage of the 2,5'-ether linkage. 2-[14C]-anAZT was incubated with a human liver homogenate or H9 leukemic cells for up to 30 hr, and at varying intervals of time, aliquots were removed, extracted with 60% methanol, and subjected to HPLC analysis. Incubation of anAZT with H9 cells produced no apparent cleavage of the ether bond. Incubation with a human liver homogenate (in 0.1% Triton X-100) resulted in cleavage of the anhydro-linkage with formation of thymine (thy). The presence of EDTA (10 mM) in the supernatant (2000 xg for 30 min) of liver homogenate enhanced the conversion of thy. Incubation of the supernatant in the presence of varying concentrations of nonradioactive AZT, but not of thy, resulted in the inhibition of the cleavage of anAZT; approx an equimolar concentration of AZT produced about 50% inhibition of the cleavage of anAZT. The reaction pathway, thus, appears to be an initial conversion of anAZT to AZT, with subsequent cleavage of AZT to form free thy.
Keywords: Biotransformation Carbon Radioisotopes Cell Line Chromatography, High Pressure Liquid Edetic Acid/PHARMACOLOGY Human Kinetics Leukemia Liver/*METABOLISM Radioisotope Dilution Technique Zidovudine/*ANALOGS & DERIVATIVES/*METABOLISM ABSTRACTKWDbiotransformationcarbonradioisotopescelllinechromatography,highpressureliquidedeticacid/pharmacologyhumankineticsleukemialiver/KWDmetabolismradioisotopedilutiontechniquezidovudine/KWDanalogs&derivatives/KWDmetabolismabstract
920730
M9271108

Copyright © 1992 - National Library of Medicine. Reproduced under license with the National Library of Medicine, Bethesda, MD.

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