Derivatives of amphotericin inhibit infection with human immunodeficiency virus in vitro by different modes of action

Three water-soluble derivatives of amphotericin B were tested for inhibition of HIV infection in vitro. The compounds amphotericin B methyl ester (AME) and N-(N′-(2-(4′-methylmorpholinio)ethyl)N″-cyclohexyl guanyl) amphotericin B methyl ester (MCG) inhibited HIV infection by 50% at 1 μg/ml; N-(N′-(3-dimethylaminopropyl)N″-ethyl guanyl) amphotericin B (DAPEG) did so at 5–11 μg/ml. While the virus-inhibitory effect of AME was due to an interaction with target lymphocytes, the effect of MCG was due to a direct anti-viral action. AME increased the potential of infected cells to fuse with uninfected cells, but MCG had no significant effect on cell fusion. All compounds had a lower cellular toxicity than amphotericin B and were not toxic at concentrations below 20 μg/ml.