Comparative analysis of anti-human immunodeficiency virus type 1 activities of dideoxynucleoside analogs in resting and activated peripheral blood mononuclear cells.
We determined the anti-human immunodeficiency virus type 1 (anti-HIV-1) activities of various dideoxy-nucleoside analogs by using phytohemagglutinin-activated peripheral blood mononuclear cells (PHA-PBMs) and resting PBMs (R-PBMs) as target cells. The comparative order of anti-HIV-1 activity in PHA-PBMs was azidothymidine (AZT) > dideoxycytidine (ddC) > dideoxythymidinene (d4T) > dideoxyinosine (ddI) and 9-(2-phosphonylmethoxyethyl)adenine (PMEA) > 2'-beta-fluoro-dideoxyadenosine (F-ara-ddA), while that in R-PBMs was ddC > ddI, PMEA, and F-ara-ddA, >> AZT and d4T. A pronucleotide, bis-(S-acetylthioethanol)phosphotriester-ddAMP, which bypasses the anabolic monophosphorylation step for the intracellular delivery of ddAMP, was highly active both in PHA-PBMs and R-PBMs. These data may have basic and clinical relevance in the design of anti-HIV chemotherapy, particularly combination chemotherapy with dideoxynucleosides, and in the development of active pronucleotides.
Shirasaka
T
T
Experimental Retrovirology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Chokekijchai
S
S
Yamada
A
A
Gosselin
G
G
Imbach
J L
JL
Mitsuya
H
H
D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D015224:Dideoxynucleosides / Q000494:pharmacology*; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D009000:Monocytes / Q000187:drug effects / Q000502:physiology / Q000821:virology*; D010835:Phytohemagglutinins / Q000494:pharmacology
D000998:Antiviral Agents; D015224:Dideoxynucleosides; D016655:HIV Core Protein p24; D010835:Phytohemagglutinins