Anti-human immunodeficiency virus type 1 activity and in vitro toxicity of 2'-deoxy-3'-thiacytidine (BCH-189), a novel heterocyclic nucleoside analog.
We describe a novel nucleoside analog, 2'-deoxy-3'-thiacytidine (BCH-189), in which the 3' carbon of the ribose ring of 2'-deoxycytidine has been replaced by a sulfur atom. In MT-4 T cells, this compound had significant time- and dose-dependent antiviral activity against five different strains of human immunodeficiency virus type 1 (HIV-1) (mean 50% inhibitory dose, 0.73 microM); known 3'-azido-3'-deoxythymidine (AZT)-resistant HIV-1 variants did not exhibit cross-resistance to it. BCH-189 also suppressed HIV-1 replication in the U937 monocytoid cell line as well as in primary cultures of human peripheral blood mononuclear cells; in these latter systems, suppression was fuller and longer lasting than that induced by AZT. Moreover, BCH-189 was less toxic than AZT in cell culture. BCH-189 may be a promising drug for the treatment of HIV-1-associated disease.
Soudeyns
H
H
Lady Davis Institute-Jewish General Hospital, Montreal, Quebec, Canada.
Yao
X I
XI
Gao
Q
Q
Belleau
B
B
Kraus
J L
JL
Nguyen-Ba
N
N
Spira
B
B
Wainberg
M A
MA
D000998:Antiviral Agents / Q000494:pharmacology* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003596:Cytosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D019259:Lamivudine; D008826:Microbial Sensitivity Tests; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000382:microbiology; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000494:pharmacology
D000998:Antiviral Agents; D019259:Lamivudine; D015215:Zidovudine; D003596:Cytosine