Anti-HIV-1 activity of sulfated amphotericin B in vitro.
To reduce the toxicity of amphotericin B methyl ester (AME), which shows some anti-HIV-1 activity, sulfated amphotericin B (SAB) was prepared from amphotericin B (AB), and its anti-HIV-1 activity was examined in vitro. SAB at concentration of 7.8 micrograms/ml completely suppressed the HIV-1-induced cytopathic effect in MT-4 cells, at 3.9 micrograms/ml inhibited the expression of HIV-1 antigen in peripheral blood mononuclear cells infected with freshly isolated HIV-1 and at 22 micrograms/ml completely suppressed formation of giant cells in cocultures of MOLT-4 with MOLT-4/HIV-1 cells. Reverse transcriptase activity was inhibited by SAB, but only at higher concentrations (0.2-1 mg/ml). Furthermore, the toxicity of SAB was lower than that of AME or AB, and SAB did not affect the proliferation of MT-4 cells at concentrations up to 0.5 mg/ml. The anti-coagulant effect of SAB was 10-fold less than that of dextran sulfate (MW = 8000). The anti-HIV-1 effect of SAB is attributed to inhibition of binding of virions to target cells.
Otake
T
T
Osaka Prefectural Institute of Public Health, Japan.
Miyano
K
K
Mori
H
H
Morimoto
M
M
Ueba
N
N
Kunita
N
N
Nakashima
H
H
Kurimura
T
T
D000666:Amphotericin B / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D003588:Cytopathogenic Effect, Viral; D016264:Dextran Sulfate / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D013601:T-Lymphocytes; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; C017501:methylamphotericin B; D000666:Amphotericin B; D016264:Dextran Sulfate