Comparison of the DNA incorporation in human MOLT-4 cells of two 2'-beta-fluoronucleosides, 2'-beta-fluoro-2',3'-dideoxyadenosine and fialuridine

被引：4

作者：

Ahluwalia, GS ^{[1
]}

Driscoll, JS ^{[1
]}

Ford, H ^{[1
]}

Johns, DG ^{[1
]}

机构：

[1] NCI,MED CHEM LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892

来源：

JOURNAL OF PHARMACEUTICAL SCIENCES | 1996年 / 85卷 / 04期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1021/js950494b

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Incorporation of 2'-beta-fluoro-2',3'-dideoxyadenosine (F-ddA), a recently developed anti-HIV agent, into the cellular DNA of human MOLT-4 cells has been compared with the DNA incorporation seen with fialuridine (FIAU; 1-[2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl]-5-iodouracil), a potent anti-hepatitis B (anti-HBV) nucleoside analogue recently found to cause severe hepatic toxicity in human subjects. At equimolar concentrations (10 mu M), incorporation of F-ddA was less than 1% of that for FIAU, a difference attributable to the lack of a 3'-hydroxyl group in the former compound and a consequent inability of F-ddA, unlike FIAU, to form DNA internucleotide linkages.

引用

页码：454 / 455

页数：2

共 13 条

[1]

BOYLE MJ, 1995, J IMMUNOL, V154, P6612

[2] CELLULAR AND MOLECULE EVENTS LEADING TO MITOCHONDRIAL TOXICITY OF 1-(2-DEOXY-2-FLUORO-1-BETA-D-ARABINOFURANOSYL)-5-LODOURACIL IN HUMAN LIVER-CELLS [J].

CUI, LX ;

YOON, SY ;

SCHINAZI, RF ;

SOMMADOSSI, JP .

JOURNAL OF CLINICAL INVESTIGATION, 1995, 95 (02) :555-563

[3] THE INTRACELLULAR PHOSPHORYLATION OF (-)-2'-DEOXY-3'-THIACYTIDINE (3TC) AND THE INCORPORATION OF 3TC 5'-MONOPHOSPHATE INTO DNA BY HIV-1 REVERSE TRANSCRIPTASE AND HUMAN DNA-POLYMERASE-GAMMA [J].

GRAY, NM ;

MARR, CLP ;

PENN, CR ;

CAMERON, JM ;

BETHELL, RC .

BIOCHEMICAL PHARMACOLOGY, 1995, 50 (07) :1043-1051

[4] Biochemical pharmacology of 2 '-fluoro-2 ',3 '-dideoxyarabinosyladenine, an inhibitor of HIV with improved metabolic and chemical stability over 2 ',3 '-dideoxyadenosine [J].

Hitchcock, M. J. M. ;

Woods, K. ;

De Boeck, H. ;

Ho, H-T .

ANTIVIRAL CHEMISTRY & CHEMOTHERAPY, 1990, 1 (05) :319-327

[5]

KENNELL D, 1967, METHOD ENZYMOL, V12, P686

[6] MITOCHONDRIAL TOXICITY OF ANTIVIRAL DRUGS [J].

LEWIS, W ;

DALAKAS, MC .

NATURE MEDICINE, 1995, 1 (05) :417-422

[7] 2',3'-DIDEOXY-2'-FLUORO-ARA-A - AN ACID-STABLE PURINE NUCLEOSIDE ACTIVE AGAINST HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) [J].

MARQUEZ, VE ;

TSENG, CKH ;

KELLEY, JA ;

MITSUYA, H ;

BRODER, S ;

ROTH, JS ;

DRISCOLL, JS .

BIOCHEMICAL PHARMACOLOGY, 1987, 36 (17) :2719-2722

[8] ACID-STABLE 2'-FLUORO PURINE DIDEOXYNUCLEOSIDES AS ACTIVE AGENTS AGAINST HIV [J].

MARQUEZ, VE ;

TSENG, CKH ;

MITSUYA, H ;

AOKI, S ;

KELLEY, JA ;

FORD, H ;

ROTH, JS ;

BRODER, S ;

JOHNS, DG ;

DRISCOLL, JS .

JOURNAL OF MEDICINAL CHEMISTRY, 1990, 33 (03) :978-985

[9]

MASOOD R, 1990, MOL PHARMACOL, V37, P590

[10] HEPATIC-FAILURE AND LACTIC-ACIDOSIS DUE TO FIALURIDINE (FIAU), AN INVESTIGATIONAL NUCLEOSIDE ANALOG FOR CHRONIC HEPATITIS-B [J].

MCKENZIE, R ;

FRIED, MW ;

SALLIE, R ;

CONJEEVARAM, H ;

DIBISCEGLIE, AM ;

PARK, Y ;

SAVARESE, B ;

KLEINER, D ;

TSOKOS, M ;

LUCIANO, C ;

PRUETT, T ;

STOTKA, JL ;

STRAUS, SE ;

HOOFNAGLE, JH .

NEW ENGLAND JOURNAL OF MEDICINE, 1995, 333 (17) :1099-1105

← 1 2 →