| pubmed-article:9661024 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:9661024 | lifeskim:mentions | umls-concept:C0682458 | lld:lifeskim |
| pubmed-article:9661024 | lifeskim:mentions | umls-concept:C0025519 | lld:lifeskim |
| pubmed-article:9661024 | lifeskim:mentions | umls-concept:C0441655 | lld:lifeskim |
| pubmed-article:9661024 | lifeskim:mentions | umls-concept:C1533691 | lld:lifeskim |
| pubmed-article:9661024 | lifeskim:mentions | umls-concept:C0205195 | lld:lifeskim |
| pubmed-article:9661024 | lifeskim:mentions | umls-concept:C0205540 | lld:lifeskim |
| pubmed-article:9661024 | lifeskim:mentions | umls-concept:C1579410 | lld:lifeskim |
| pubmed-article:9661024 | lifeskim:mentions | umls-concept:C0049181 | lld:lifeskim |
| pubmed-article:9661024 | pubmed:issue | 7 | lld:pubmed |
| pubmed-article:9661024 | pubmed:dateCreated | 1998-10-8 | lld:pubmed |
| pubmed-article:9661024 | pubmed:abstractText | 2',3'-Dideoxy-2',3'-didehydro-beta-L(-)-5-fluorocytidine [L(-)Fd4C] has been reported to be a potent inhibitor of the human immunodeficiency virus (HIV) in cell culture. In the present study the antiviral activity of this compound in two-drug combinations and its intracellular metabolism are addressed. The two-drug combination of L(-)Fd4C plus 2',3'-didehydro-2'-3'-dideoxythymidine (D4T, or stavudine) or 3'-azido-3'-deoxythymidine (AZT, or zidovudine) synergistically inhibited replication of HIV in vitro. Additive antiviral activity was observed with L(-)Fd4C in combination with 2',3'-dideoxycytidine (ddC, or zalcitabine) or 2',3'-dideoxyinosine (ddI, or didanosine). This beta-L(-) nucleoside analog has no activity against mitochondrial DNA synthesis at concentrations up to 10 microM. As we previously reported for other beta-L(-) nucleoside analogs, L(-)Fd4C could protect against mitochondrial toxicity associated with D4T, ddC, and ddI. Metabolism studies showed that this drug is converted intracellularly to its mono-, di-, and triphosphate metabolites. The enzyme responsible for monophosphate formation was identified as cytoplasmic deoxycytidine kinase, and the K(m) is 100 microM. L(-)Fd4C was not recognized in vitro by human mitochondrial deoxypyrimidine nucleoside kinase. Also, L(-)Fd4C was not a substrate for deoxycytidine deaminase. L(-)Fd4C 5'-triphosphate served as an alternative substrate to dCTP for incorporation into DNA by HIV reverse transcriptase. The favorable anti-HIV activity and protection from mitochondrial toxicity by L(-)Fd4C in two-drug combinations favors the further development of L(-)Fd4C as an anti-HIV agent. | lld:pubmed |
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| pubmed-article:9661024 | pubmed:language | eng | lld:pubmed |
| pubmed-article:9661024 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:9661024 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:9661024 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:9661024 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:9661024 | pubmed:month | Jul | lld:pubmed |
| pubmed-article:9661024 | pubmed:issn | 0066-4804 | lld:pubmed |
| pubmed-article:9661024 | pubmed:author | pubmed-author:LiuS HSH | lld:pubmed |
| pubmed-article:9661024 | pubmed:author | pubmed-author:GuyRR | lld:pubmed |
| pubmed-article:9661024 | pubmed:author | pubmed-author:ChengY CYC | lld:pubmed |
| pubmed-article:9661024 | pubmed:author | pubmed-author:KukhanovaMM | lld:pubmed |
| pubmed-article:9661024 | pubmed:author | pubmed-author:DutschmanG... | lld:pubmed |
| pubmed-article:9661024 | pubmed:author | pubmed-author:BridgesE GEG | lld:pubmed |
| pubmed-article:9661024 | pubmed:author | pubmed-author:GullenEE | lld:pubmed |
| pubmed-article:9661024 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:9661024 | pubmed:volume | 42 | lld:pubmed |
| pubmed-article:9661024 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:9661024 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:9661024 | pubmed:pagination | 1799-804 | lld:pubmed |
| pubmed-article:9661024 | pubmed:dateRevised | 2009-11-18 | lld:pubmed |
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| pubmed-article:9661024 | pubmed:meshHeading | pubmed-meshheading:9661024-... | lld:pubmed |
| pubmed-article:9661024 | pubmed:year | 1998 | lld:pubmed |
