Anacolosins A-F and Corymbulosins X and Y, Clerodane Diterpenes from Anacolosa clarkii Exhibiting Cytotoxicity toward Pediatric Cancer Cell Lines

Shengxin Cai, April L Risinger, Cora L. Petersen, Tanja Grkovic, Barry R. O'Keefe, Susan L Mooberry, Robert H. Cichewicz

Research output: Contribution to journalArticle

Abstract

An extract of the plant Anacolosa clarkii was obtained from the NCI Natural Products Repository, and it showed cytotoxic activity toward several types of pediatric solid tumor cell lines. Bioassay-guided fractionation led to the purification of eight new clerodane diterpenes [anacolosins A-F (1-6) and corymbulosins X and Y (7 and 8)] and two known compounds (9 and 10) that contained an isozuelanin skeleton. The structures of the new natural products were determined using 1D and 2D NMR and HRESIMS data, while the relative and absolute configurations of the compounds were assessed using a combination of 1 H NMR coupling constant data, ROESY experiments, ECD (electronic circular dichroism) and VCD (vibrational circular dichroism) spectroscopy, chemical methods (including Mosher and 2-naphthacyl esterification), and chiral HPLC analyses. The purified natural products exhibited a range of cytotoxic activities against cell lines representing four pediatric cancer types (i.e., rhabdomyosarcoma, Ewing sarcoma, medulloblastoma, and hepatoblastoma) with total growth inhibitory (TGI) values in the range 0.2-4.1 μM. The rhabdomyosarcoma and medulloblastoma cell lines showed higher sensitivity to compounds 1-4, which are the first compounds reported to contain an isozuelanin skeleton and feature keto carbonyl groups at the C-6 positions. In contrast, the hepatoblastoma cell line was modestly more sensitive to 7-10, which contained a C-6 hydroxy group moiety.

Original languageEnglish (US)
JournalJournal of Natural Products
DOIs
StatePublished - Jan 1 2019

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Clerodane Diterpenes
Pediatrics
Cytotoxicity
Biological Products
Hepatoblastoma
Medulloblastoma
Rhabdomyosarcoma
Cells
Circular Dichroism
Skeleton
Cell Line
Neoplasms
Ewing's Sarcoma
Esterification
Plant Extracts
Nuclear magnetic resonance
Circular dichroism spectroscopy
Tumor Cell Line
Biological Assay
Vibrational spectroscopy

ASJC Scopus subject areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

Cite this

Anacolosins A-F and Corymbulosins X and Y, Clerodane Diterpenes from Anacolosa clarkii Exhibiting Cytotoxicity toward Pediatric Cancer Cell Lines. / Cai, Shengxin; Risinger, April L; Petersen, Cora L.; Grkovic, Tanja; O'Keefe, Barry R.; Mooberry, Susan L; Cichewicz, Robert H.

In: Journal of Natural Products, 01.01.2019.

Research output: Contribution to journalArticle

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