Favorable interactions between enfuvirtide and 1-beta-D-2,6-diaminopurine dioxolane in vitro.
نویسندگان
چکیده
We evaluated the in vitro anti-human immunodeficiency virus type 1 (HIV-1) interactions between 1-beta-D-2,6-diaminopurine dioxolane (DAPD) and enfuvirtide (T-20) against clinical isolates sensitive and resistant to reverse transcriptase and protease inhibitors. Interactions between T-20 and DAPD were synergistic to nearly additive, with combination index values ranging from 0.53 to 1.06 at 95% inhibitory concentrations. These studies suggest that a combination of T-20 and DAPD might be useful in the treatment of antiretroviral drug-experienced patients.
منابع مشابه
Mechanism of action of 1-beta-D-2,6-diaminopurine dioxolane, a prodrug of the human immunodeficiency virus type 1 inhibitor 1-beta-D-dioxolane guanosine.
(-)-beta-D-2,6-Diaminopurine dioxolane (DAPD), is a nucleoside reverse transcriptase (RT) inhibitor with activity against human immunodeficiency virus type 1 (HIV-1). DAPD, which was designed as a water-soluble prodrug, is deaminated by adenosine deaminase to give (-)-beta-D-dioxolane guanine (DXG). By using calf adenosine deaminase a K(m) value of 15 +/- 0.7 microM was determined for DAPD, whi...
متن کاملAttempt to reduce cytotoxicity by synthesizing the L-enantiomer of 4'-C-ethynyl-2'-deoxypurine nucleosides as antiviral agents against HIV and HBV.
We investigated the potential of 4'-C-substituted nucleosides for the treatment of HIV-1 and HBV. Of the nucleosides we prepared, several 4'-C-ethynyl-2'-deoxypurine nucleosides showed the most potent anti-HIV activity. However, two candidates, 4'-C-ethynyl-2'-deoxyguanosine and 9-(2-deoxy-4-C-ethynyl-beta-D-ribo-pentofuranosyl)-2,6-diaminopurine, were very toxic during in vivo study. On the ot...
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PHILLIP A. FURMAN,* JERRY JEFFREY, LAURA L. KIEFER, JOY Y. FENG, KAREN S. ANDERSON, KATYNA BORROTO-ESODA, EDGAR HILL, WILLIAM C. COPELAND, CHUNG K. CHU, JEAN-PIERRE SOMMADOSSI, IRINA LIBERMAN, RAYMOND F. SCHINAZI, AND GEORGE R. PAINTER Triangle Pharmaceuticals, Durham, North Carolina 27707; Department of Pharmacology, Yale School of Medicine, New Haven, Connecticut 06520-8066; Laboratory of Mol...
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Modified nucleotides are useful tools to study the structures, biological functions and chemical and thermodynamic stabilities of nucleic acids. Derivatives of 2,6-diaminopurine riboside (D) are one type of modified nucleotide. The presence of an additional amino group at position 2 relative to adenine results in formation of a third hydrogen bond when interacting with uridine. New method for c...
متن کاملAntagonism studies with several toxic purines and purine nucleosides in mouse tissue cultures.
The possibility that the nucleic acid metabolism of cancer cells differs sufficiently from that of nor mal cells to allow a selective inhibition of cancer cell growth by means of agents that intervene at one stage or another in nucleic acid metabolism has led to numerous recent investigations (5, 7—10, 12—14, 16—19).Among the agents tested have been purine derivatives and analogs. 2,6-Dia...
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ورودعنوان ژورنال:
- Antimicrobial agents and chemotherapy
دوره 47 11 شماره
صفحات -
تاریخ انتشار 2003