title: Derivatives of amphotericin inhibit infection with human immunodeficiency virus in vitro by different modes of action.
abstract: 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 microgram/ml; N-(N'-(3-dimethylaminopropyl)N"-ethyl guanyl) amphotericin B (DAPEG) did so at 5-11 micrograms/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 micrograms/ml.
authors.affiliation: Department of Infectious Diseases, Hvidovre Hospital, Denmark.
authors.forename: J E
authors.initials: JE
authors.lastname: Hansen
authors.forename: N M
authors.initials: NM
authors.lastname: Witzke
authors.forename: C
authors.initials: C
authors.lastname: Nielsen
authors.forename: L R
authors.initials: LR
authors.lastname: Mathiesen
authors.forename: L S
authors.initials: LS
authors.lastname: Teglbjaerg
authors.forename: C M
authors.initials: CM
authors.lastname: Nielsen
authors.forename: J O
authors.initials: JO
authors.lastname: Nielsen
mesh_terms: D000666:Amphotericin B / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D002459:Cell Fusion / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015726:Giant Cells / Q000187:drug effects; D015488:HIV Antigens / Q000032:analysis; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans
chemical_list: D015488:HIV Antigens; C017501:methylamphotericin B; C067384:N-(N'-(2-(4'-methylmorpholinio)ethyl)-N''-cyclohexylguanyl)amphotericin B methyl ester; D000666:Amphotericin B; C038420:amphotericin B, N-(N'-(3-dimethylaminopropyl)-N''-ethylguanyl)-