Antiretroviral Chemotherapy of Human Immunodeficiency Virus Infections Other Than With Azidothymidine

Sachs, Mark K.

doi:10.1001/archinte.1992.00400150019005

Cited by 11 publications

(2 citation statements)

References 118 publications

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“…In the last several years, active pursuit of effective anti-HBV agents has resulted in the identification of a number of poten-tially useful nucleoside analogs, and a number of them that are active against human immunodeficiency virus are currently used in clinics for the treatment of patients with AIDS (15,28,33). Upon long-term usage, these analogs have delayed toxicity, on the basis of clinical experience.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of hepatitis B virus by a novel L-nucleoside, 2'-fluoro-5-methyl-beta-L-arabinofuranosyl uracil

Pai

Liu

Zhu

et al. 1996

Antimicrob Agents Chemother

138

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2'-Fluoro-5-methyl-beta-L-arabinofuranosyl uracil (L-FMAU) was discovered to have potent antiviral activity against hepatitis B virus (HBV). L-FMAU was more potent than its D-enantiomer and produced dose-dependent inhibition of the viral DNA replication in 2.2.15 cells (human HepG2 cells with the HBV genome), with a 50% inhibitory concentration of 0.1 microM. There was no inhibitory effect on HBV transcription or protein synthesis. In the 2.2.15 cell system, L-FMAU did not show any toxicity up to 200 microM, whereas the D-enantiomer was toxic, with a 50% inhibitory concentration of 50 microM. Repeated treatments of HepG2 cells with L-FMAU at a 1 microM concentration for 9 days did not result in any decrease in the total mitochondrial DNA content, suggesting that a mode of toxicity similar to that produced by 2',3'-dideoxycytidine is unlikely. Also at concentrations as high as 200 microM, L-FMAU did not adversely affect mitochondrial function as determined by lactic acid production by L-FMAU-treated hepatoma cells. L-FMAU was metabolized in the cells to its mono-, di-, and triphosphates, A dose-dependent inhibition of HBV DNA synthesis by L-FMAU triphosphate was observed in the DNA polymerase assays with isolated HBV particles, suggesting that the mode of action of this compound could involve viral polymerase. However, L-FMAU was not incorporated into the cellular DNA. Considering the potent inhibition of the viral DNA synthesis and the nontoxicity of L-FMAU towards the host DNA synthetic machinery, this compound should be further explored for development as asn anti-HBV drug.

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Section: Discussionmentioning

confidence: 99%

Inhibition of hepatitis B virus by a novel L-nucleoside, 2'-fluoro-5-methyl-beta-L-arabinofuranosyl uracil

Pai

Liu

Zhu

et al. 1996

Antimicrob Agents Chemother

138

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“…The initial discovery of marine nucleosides can be traced back to the identifications of spongothymidine and spongouridine in the early 1950s from the Caribbean sponge Tethyacrypta [8–9], which subsqeuently led to the commercialization of arabinofuranosylcytosine (Ara-C) [10], arabinofuranosyladenine (Ara-A) [11], and azidothymidine (AZT) [12] for clinical use.…”

Section: Introductionmentioning

confidence: 99%

Concise total synthesis of two marine natural nucleosides: trachycladines A and B

Ding¹,

Li²,

Ruan³

et al. 2014

Beilstein J. Org. Chem.

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SummaryWe report the first total synthesis of trachycladines A (10 steps, 34.2% overall yield) and B (11 steps, 35.0% overall yield) by using 5-deoxy-1,2,3-tri-O-acetyl-β-D-ribofuranose as the starting material. The critical step was the SnCl4 assisted regio- and steroselective deprotection of perbenzylated 1-O-methyl-5-deoxyribofuranose. The enzyme adenylate deaminase (EC 3.5.4.6) was successfully applied to the chemoenzymatic synthesis of trachycladines B.

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Preventive Health Care for Adults With HIV Infection

Jewett

Hecht²

1993

JAMA

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Antiretroviral Chemotherapy of Human Immunodeficiency Virus Infections Other Than With Azidothymidine

Cited by 11 publications

References 118 publications

Inhibition of hepatitis B virus by a novel L-nucleoside, 2'-fluoro-5-methyl-beta-L-arabinofuranosyl uracil

Inhibition of hepatitis B virus by a novel L-nucleoside, 2'-fluoro-5-methyl-beta-L-arabinofuranosyl uracil

Concise total synthesis of two marine natural nucleosides: trachycladines A and B

Preventive Health Care for Adults With HIV Infection

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