Anti-HIV michellamines from Ancistrocladus korupensis.
Here we report details of the isolation and determination of the absolute configurations and comparative anti-HIV activities of novel, atropisomeric naphthylisoquinoline alkaloid dimers, michellamines A, B, and C, from a newly described species of Ancistrocladus from the Korup rainforest of Cameroon. We further provide a more extensive analysis of the range of anti-HIV activity of michellamine B, the most potent and abundant member of the series. Michellamine B inhibited HIV-induced cell killing and viral replication in a variety of human cell lines, as well as in cultures of human peripheral blood leukocytes and monocytes. Michellamine B was active against a panel of biologically diverse laboratory and clinical strains of HIV-1, including the AZT-resistant strain G910-6 and the pyridinone-resistant strain A17; the compound also inhibited several strains of HIV-2.
Laboratory of Drug Discovery Research & Development, National Cancer Institute-Frederick Cancer Research & Development Center, Maryland 21702-1201.
M R
MR
Boyd
Y F
YF
Hallock
J H
JH
Cardellina
K P
KP
Manfredi
J W
JW
Blunt
J B
JB
McMahon
R W
RW
Buckheit
G
G
Bringmann
M
M
Schäffer
G M
GM
Cragg
D000349:Africa; D000998:Antiviral Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002478:Cells, Cultured; D004347:Drug Interactions; D006678:HIV / Q000187:drug effects* / Q000502:physiology; D015497:HIV-1 / Q000187:drug effects; D015498:HIV-2 / Q000187:drug effects; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009281:Naphthalenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010944:Plants / Q000737:chemistry*; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000494:pharmacology
D000998:Antiviral Agents; D007546:Isoquinolines; D009281:Naphthalenes; C072235:michellamine A; D015215:Zidovudine