Chiral resolution of a caged xanthone and evaluation across a broad spectrum of breast cancer subtypes

Oraphin Chantarasriwong; Tanis J Dorwart; Theodore Habarth Morales; Stephanie F Maggio; Aspen L Settle; Andrew T Milcarek; Mary L Alpaugh; Maria A Theodoraki; Emmanuel A Theodorakis

doi:10.1016/j.bioorg.2019.103303

Chiral resolution of a caged xanthone and evaluation across a broad spectrum of breast cancer subtypes

Bioorg Chem. 2019 Dec:93:103303. doi: 10.1016/j.bioorg.2019.103303. Epub 2019 Sep 21.

Authors

Oraphin Chantarasriwong¹, Tanis J Dorwart², Theodore Habarth Morales², Stephanie F Maggio², Aspen L Settle², Andrew T Milcarek³, Mary L Alpaugh⁴, Maria A Theodoraki⁵, Emmanuel A Theodorakis⁶

Affiliations

¹ Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0358, USA; Department of Chemistry, Faculty of Science, King Mongkut's University of Technology Thonburi, 126 Pracha Uthit Rd., Bang Mod, Thung Khru, Bangkok 10140, Thailand.
² Department of Biology, Arcadia University, Glenside, PA 19038, USA.
³ Department of Molecular and Cellular Biosciences, Rowan University, Glassboro, NJ 08028, USA.
⁴ Department of Molecular and Cellular Biosciences, Rowan University, Glassboro, NJ 08028, USA. Electronic address: [email protected].
⁵ Department of Biology, Arcadia University, Glenside, PA 19038, USA. Electronic address: [email protected].
⁶ Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0358, USA. Electronic address: [email protected].

PMID: 31585264
DOI: 10.1016/j.bioorg.2019.103303

Abstract

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.

Keywords: Breast cancer; Gambogic acid; Garcinia; Natural product; Synthetic methods.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry*
Antineoplastic Agents / pharmacology
Breast Neoplasms / metabolism
Breast Neoplasms / pathology
Cell Line, Tumor
Cell Survival / drug effects
Crystallography, X-Ray
Drug Screening Assays, Antitumor
Female
Humans
Molecular Conformation
Stereoisomerism
Xanthones / chemical synthesis
Xanthones / chemistry*
Xanthones / pharmacology

Substances

Antineoplastic Agents
Xanthones