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Synthesis, and in vitro enzymatic and antiviral evaluation of d4T polyphosphate derivatives as chain terminators.
- Source :
-
Chemistry & biodiversity [Chem Biodivers] 2012 Oct; Vol. 9 (10), pp. 2186-94. - Publication Year :
- 2012
-
Abstract
- A series of d4T di- or triphosphate derivatives have been synthesized and evaluated as effective substrates for HIV-1 RT, and also tested for their in vitro anti-HIV activity. The steady-state kinetic study of compounds 1-4 in an enzymatic incorporation assay by HIV-1 RT follows Michaelis-Menten profile. In addition, compounds 2-4 are able to inhibit HIV-1 replication to the same extent as d4T and d4TMP in MT-4 cells, as well as in CEM/0 cells and CEM/TK(-) cells. The data suggests that these d4T polyphosphate derivatives are hydrolyzed to d4T and rephosphorylated to d4TTP before exerting their antiviral activity.<br /> (Copyright © 2012 Verlag Helvetica Chimica Acta AG, Zürich.)
- Subjects :
- Anti-HIV Agents chemical synthesis
Anti-HIV Agents pharmacology
Cell Line
Dideoxynucleotides chemical synthesis
Dideoxynucleotides pharmacology
HIV Reverse Transcriptase antagonists & inhibitors
HIV Reverse Transcriptase metabolism
HIV-1 metabolism
Humans
Kinetics
Stavudine chemical synthesis
Stavudine pharmacology
Thymidine Monophosphate chemistry
Thymidine Monophosphate pharmacology
Virus Replication drug effects
Anti-HIV Agents chemistry
Dideoxynucleotides chemistry
Polyphosphates chemistry
Stavudine analogs & derivatives
Thymidine Monophosphate chemical synthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1612-1880
- Volume :
- 9
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Chemistry & biodiversity
- Publication Type :
- Academic Journal
- Accession number :
- 23081918
- Full Text :
- https://doi.org/10.1002/cbdv.201200250