A pentahalogenated monoterpene from the red alga Portieria hornemannii produces a novel cytotoxicity profile against a diverse panel of human tumor cell lines.
A polyhalogenated acyclic monoterpene, 6(R)-bromo-3(S)-(bromomethyl)-7- methyl-2,3,7-trichloro-1-octene (1) was obtained as a major component of the organic extract of the red alga Portieria hornemannii. X-ray diffraction analysis provided the complete structure, including correct placement of the different halogen atoms and determination of the absolute stereochemistry. Detailed NMR analyses provided complete 1H and 13C assignments. Compound 1 exhibited highly differential cytotoxicity against the U.S. National Cancer Institute's new in vitro human tumor cell line screening panel; brain tumor, renal, and colon tumor cell lines were most sensitive to 1, while leukemia and melanoma lines were relatively less sensitive. A second collection of P. hornemanni yielded the novel, monocyclic 2, considerably less cytotoxic and devoid of differential activity. On the basis of its unprecedented cytotoxicity profile in the NCI primary screen, compound 1 has been selected by the NCI Decision Network Committee for preclinical drug development.
Fuller
R W
RW
Laboratory of Drug Discovery Research and Development, National Cancer Institute, Frederick Cancer Research & Development Center, Maryland 21702-1201.
Cardellina
J H
JH
Kato
Y
Y
Brinen
L S
LS
Clardy
J
J
Snader
K M
KM
Boyd
M R
MR
D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006846:Hydrocarbons, Halogenated / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008958:Models, Molecular; D000461:Rhodophyta / Q000737:chemistry*; D014407:Tumor Cells, Cultured; D014961:X-Ray Diffraction
D000970:Antineoplastic Agents; D006846:Hydrocarbons, Halogenated; C076123:6-bromo-3-(bromomethyl)-7-methyl-2,3,7-trichloro-1-octene