TY - JOUR
T1 - Chiral resolution of a caged xanthone and evaluation across a broad spectrum of breast cancer subtypes
AU - Chantarasriwong, Oraphin
AU - Dorwart, Tanis J.
AU - Morales, Theodore Habarth
AU - Maggio, Stephanie F.
AU - Settle, Aspen L.
AU - Milcarek, Andrew T.
AU - Alpaugh, Mary L.
AU - Theodoraki, Maria A.
AU - Theodorakis, Emmanuel A.
N1 - Funding Information:
We thank the financial support of the California Breast Cancer Research Program (IDEA Award No: 22IB-0024). This work was also supported by the Ellington Beavers Award from Arcadia University. We also thank Professor T. F. Molinski (UCSD) for access to his chiral HPLC columns and Teresa Abendroth for editorial assistance.
Funding Information:
We thank the financial support of the California Breast Cancer Research Program (IDEA Award No: 22IB-0024). This work was also supported by the Ellington Beavers Award from Arcadia University . We also thank Professor T. F. Molinski (UCSD) for access to his chiral HPLC columns and Teresa Abendroth for editorial assistance.
PY - 2019/12
Y1 - 2019/12
N2 - Racemic resolution of (+/−)-MAD28, a representative caged xanthone, was accomplished using (1S, 4R)-(−)-camphanic chloride as the chiral agent. Selective crystallization of the resulting diastereomers in acetonitrile produced, after hydrolysis, the pure enantiomers. Screening of racemic MAD28 and both enantiomers across a broad spectrum of breast cancer cell lines revealed that they: (a) are equipotent in each of the breast cancer subtypes examined; and (b) exhibit a higher degree of cytotoxicity against breast cancer cell lines of basal-like subtype and triple negative receptor status. The results support the notion that MAD28 and related caged xanthones are promising drug leads against chemoresistant and metastatic cancers.
AB - Racemic resolution of (+/−)-MAD28, a representative caged xanthone, was accomplished using (1S, 4R)-(−)-camphanic chloride as the chiral agent. Selective crystallization of the resulting diastereomers in acetonitrile produced, after hydrolysis, the pure enantiomers. Screening of racemic MAD28 and both enantiomers across a broad spectrum of breast cancer cell lines revealed that they: (a) are equipotent in each of the breast cancer subtypes examined; and (b) exhibit a higher degree of cytotoxicity against breast cancer cell lines of basal-like subtype and triple negative receptor status. The results support the notion that MAD28 and related caged xanthones are promising drug leads against chemoresistant and metastatic cancers.
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U2 - 10.1016/j.bioorg.2019.103303
DO - 10.1016/j.bioorg.2019.103303
M3 - Article
C2 - 31585264
AN - SCOPUS:85072832367
SN - 0045-2068
VL - 93
JO - Bioorganic Chemistry
JF - Bioorganic Chemistry
M1 - 103303
ER -