Antitumor activity and stereochemistry of acetylenic alcohols from the sponge Cribrochalina vasculum.
Antitumor bioassay-guided fractionation of the organic extract of the marine sponge Cribrochalina vasculum resulted in the isolation of several closely related cytotoxic acetylenic alcohols [1-8], the structures of which were assigned on the basis of chemical and spectral studies. 3-Hydroxyeicos-(4E)-en-1-yne[1], 3-hydroxydocosa-(4E,15Z)-dien-1-yne[2], 3-hydroxy-16-methyleicos-(4E)-en-1-yne[3], 3-hydroxy-19-methyleicos-(4E)-en-1-yne[4], 3-hydroxy-21-methyldocosa-(4E,15Z)-dien-1-yne [5], and 3-hydroxy-14-methyldocosa-(4E)-en-1-yne [6] are enantiomers of known compounds, while 3-hydroxyheneeicos-(4E)-en-1-yne [7] and 5-hydroxy-16-methyleicos-(3Z)-en-1-yne [8] are new metabolites isolated as minor components. The absolute configuration of C-3 in 1-7 and C-5 in 8 has been assigned as S using the modified Mosher's method. Compounds selected from this series showed selective in vitro antitumor activity against the H-522 non-small cell lung line and the IGROV-1 ovarian line. Synthetic racemic 1 demonstrated a modest dose-related therapeutic activity in a preliminary in vivo xenograft assay based on the latter cell line.
Hallock
Y F
YF
Division of Cancer Treatment, National Cancer Institute, Frederick, Maryland 21702-1201, USA.
Cardellina
J H
JH
Balaschak
M S
MS
Alexander
M R
MR
Prather
T R
TR
Shoemaker
R H
RH
Boyd
M R
MR
D000480:Alkynes / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D004354:Drug Screening Assays, Antitumor; D005233:Fatty Alcohols / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D009368:Neoplasm Transplantation; D011161:Porifera / Q000737:chemistry*; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured
D000480:Alkynes; D000970:Antineoplastic Agents; D005233:Fatty Alcohols