TY - JOUR
T1 - Synthesis and structure-activity studies of schweinfurthin B analogs
T2 - Evidence for the importance of a D-ring hydrogen bond donor in expression of differential cytotoxicity
AU - Neighbors, Jeffrey D.
AU - Salnikova, Maya S.
AU - Beutler, John A.
AU - Wiemer, David F.
N1 - Funding Information:
We thank Domenic Scudiero and the Developmental Therapeutics Program, NCI, for 60-cell testing. Financial support from the Breast Cancer Research Program (DAMD17-01-1-0276 and DAMD17-02-1-0423), the University of Iowa Graduate College, and an Oncology Research Training Award from the Holden Comprehensive Cancer Center’s Institutional National Research Service Award (2 T32 CA79445-05) is gratefully acknowledged. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.
PY - 2006/3/15
Y1 - 2006/3/15
N2 - The synthesis and biological evaluation of several enantioenriched schweinfurthin B analogs were undertaken to develop structure-activity relationships and guide design of probes for their putative molecular target. The desired stilbenes contain a common left-half hexahydroxanthene ring system and an aromatic right-half with varied substituents. The synthesis involves penultimate Horner-Wadsworth-Emmons coupling of one of several right-half phosphonates with the aldehyde comprising the left-half of 3-deoxyschweinfurthin B. Preparation of the requisite phosphonates, and the respective stilbenes, as well as the cytotoxicity profiles of these new compounds in the National Cancer Institute's 60 cell-line anticancer screen is described. Several of these analogs displayed cytotoxicity patterns well-correlated with the natural product and differences in activity of ∼103 across the various cell lines. Together, these assay results indicate the importance of at least one free phenol group on the aromatic D-ring of this system for differential cytotoxicity.
AB - The synthesis and biological evaluation of several enantioenriched schweinfurthin B analogs were undertaken to develop structure-activity relationships and guide design of probes for their putative molecular target. The desired stilbenes contain a common left-half hexahydroxanthene ring system and an aromatic right-half with varied substituents. The synthesis involves penultimate Horner-Wadsworth-Emmons coupling of one of several right-half phosphonates with the aldehyde comprising the left-half of 3-deoxyschweinfurthin B. Preparation of the requisite phosphonates, and the respective stilbenes, as well as the cytotoxicity profiles of these new compounds in the National Cancer Institute's 60 cell-line anticancer screen is described. Several of these analogs displayed cytotoxicity patterns well-correlated with the natural product and differences in activity of ∼103 across the various cell lines. Together, these assay results indicate the importance of at least one free phenol group on the aromatic D-ring of this system for differential cytotoxicity.
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U2 - 10.1016/j.bmc.2005.10.025
DO - 10.1016/j.bmc.2005.10.025
M3 - Article
C2 - 16290161
AN - SCOPUS:32044436701
SN - 0968-0896
VL - 14
SP - 1771
EP - 1784
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 6
ER -
