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PMID: 1929298 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Anti-human immunodeficiency virus type 1 activity and in vitro toxicity of 2'-deoxy-3'-thiacytidine (BCH-189), a novel heterocyclic nucleoside analog.

Antimicrobial agents and chemotherapy ·Vol. 35 ·No. 7 ·1991-07-00 ·Pages 1386-90

Soudeyns H, Yao XI, Gao Q, Belleau B, Kraus JL, Nguyen-Ba N, Spira B, Wainberg MA

Abstract

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analog, 2'-deoxy-3'-thiacytidine (BCH-189), in which the 3' carbon of the ribose ring of 2'-deoxycytidine has been replaced by a sulfur atom.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.

MeSH Terms
Antiviral Agents/pharmacology,toxicity Cell Survival/drug effects Cells, Cultured Cytosine/analogs & derivatives,pharmacology,toxicity HIV-1/drug effects Humans Lamivudine Microbial Sensitivity Tests Monocytes/drug effects,metabolism T-Lymphocytes/drug effects,microbiology Virus Replication/drug effects Zidovudine/pharmacology
Chemicals
Antiviral Agents Lamivudine Zidovudine Cytosine
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Soudeyns H
Lady Davis Institute-Jewish General Hospital, Montreal, Quebec, Canada.
Yao X I
Gao Q
Belleau B
Kraus J L
Nguyen-Ba N
Spira B
Wainberg M A
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Article Info
Journal
Antimicrobial agents and chemotherapy
Abbr.
Antimicrob Agents Chemother
ISSN
0066-4804
DOI
10.1128/AAC.35.7.1386
Published
1991-07-00
Pages
1386-90
Language
English
Region
United States
NLM ID
0315061
PMCID
PMC245177
Subset
IM
External Links
PubMed source DOI: 10.1128/AAC.35.7.1386 PMC Full Text View journal details
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