Highly specific inhibition of human immunodeficiency virus type 1 by a novel 6-substituted acyclouridine derivative.
A novel 6-substituted acyclouridine derivative, 1-[(2-hydroxy-ethoxy) methyl]-6-phenylthiothymine (HEPT), has proved to be a potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1) in vitro. HEPT inhibits HIV-1 replication in various T4 cell cultures as well as peripheral blood lymphocytes and macrophages. The 50% antiviral effective concentration for HIV-1 (HTLV-IIIB) in MT-4 cells is 7.0 microM, while the 50% cytotoxic concentration for mock-infected MT-4 cells is 740 microM. Although HEPT is inhibitory to various strains of HIV-1, it has no effect on the replication of other retroviruses including HIV type 2. In contrast with the dideoxynucleoside (i.e. azidothymidine) 5'-triphosphates, the triphosphate of HEPT does not interact with HIV-1 reverse transcriptase. The mechanism of action of HEPT remains subject of further study.
Baba
M
M
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
Tanaka
H
H
De Clercq
E
E
Pauwels
R
R
Balzarini
J
J
Schols
D
D
Nakashima
H
H
Perno
C F
CF
Walker
R T
RT
Miyasaka
T
T
D000998:Antiviral Agents; D015496:CD4-Positive T-Lymphocytes / Q000382:microbiology; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015488:HIV Antigens / Q000096:biosynthesis; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D015498:HIV-2 / Q000187:drug effects; D008214:Lymphocytes / Q000382:microbiology; D008264:Macrophages / Q000382:microbiology; D013941:Thymine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects; D016047:Zalcitabine / Q000494:pharmacology; D015215:Zidovudine / Q000494:pharmacology
D000998:Antiviral Agents; D015488:HIV Antigens; C061818:1-((2-hydroxyethoxy)methyl)-6-(phenylthio)thymine; D015215:Zidovudine; D016047:Zalcitabine; D013941:Thymine