Selective activity of several cholic acid derivatives against human immunodeficiency virus replication in vitro.
Several cholic acid derivatives such as taurolithocholic acid, lithocholic acid 3-sulfate, taurolithocholic acid 3-sulfate, and glycolithocholic acid 3-sulfate were shown to inhibit selectively the replication of human immunodeficiency virus type 1 (HIV-1) in vitro. These compounds completely protected MT-4 cells against HIV-1-induced cytopathogenicity at a concentration of 100 micrograms/ml, whereas no toxicity for the host cells was observed at 200 micrograms/ml. They also inhibited HIV-1 antigen expression in HIV-1-infected CEM cells. The bile acids (cholic acid, deoxycholic acid, chenodeoxycholic acid, and lithocholic acid) did not show any inhibitory effect on HIV-1 replication at concentrations that were not toxic to the host (MT-4) cells. From a structure-function analysis of a number of cholic acid derivatives, the presence of either a sulfonate (as in the tauro conjugates) or a sulfate group as well as the "litho" configuration appeared to be necessary for the expression of anti-HIV-1 activity. The active cholic acid derivatives did not directly inactivate the virus particles at the concentrations that were not toxic to the host cells. Lithocholic acid 3-sulfate, taurolithocholic acid 3-sulfate, and glycolithocholic acid 3-sulfate, but not taurolithocholic acid, partially inhibited virus adsorption to MT-4 cells. These three compounds were also inhibitory to the reverse transcriptase activity associated with HIV-1.
Baba
M
M
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
Schols
D
D
Nakashima
H
H
Pauwels
R
R
Parmentier
G
G
Meijer
D K
DK
De Clercq
E
E
D000327:Adsorption; D000956:Antigens, Viral / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002793:Cholic Acids / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology / Q000502:physiology; D006801:Humans; D009500:Neutralization Tests; D012194:RNA-Directed DNA Polymerase / Q000032:analysis; D014779:Virus Replication / Q000187:drug effects*
D000956:Antigens, Viral; D002793:Cholic Acids; D012194:RNA-Directed DNA Polymerase