Alteration of the bis-tetrahydrofuran core stereochemistries in asimicin can affect the cytotoxicity.
A systematic analysis using 10 synthetic asimicin stereoisomers revealed that the stereochemistry of the bis-tetrahydrofuran core, including the tetrahydrofuran rings and the adjacent hydroxy functions, had significant effect on its cytotoxicity. Our findings set to rest the highly controversial perception that the stereochemistry of the tetrahydrofuran core has little effect on the activity, which is not true for its cytotoxic effect, and also reinforces the previous conclusion that asimicin is a highly potent anticancer compound.
Sinha
Subhash C
SC
The Skaggs Institute for Chemical Biology and the Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. subhash@scripps.edu
Chen
Zhiyong
Z
Huang
Zheng-Zheng
ZZ
Nakamaru-Ogiso
Eiko
E
Pietraszkiewicz
Halina
H
Edelstein
Matthew
M
Valeriote
Frederick
F
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity*; D006801:Humans; D051379:Mice; D008968:Molecular Conformation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D005663:Furans; C061022:bullatacin; C018674:tetrahydrofuran