Daturolides A-K, cytotoxic sesquiterpene lactones from Datura wrightii.
4 affiliations
- 1Molecular Targets Program, Center for Cancer Research, National Cancer Institute Frederick Maryland 21702-1201 USA [email protected].
- 2Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute Bethesda Maryland 20892 USA.
- 3Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research Frederick Maryland 21702-1201 USA.
- 4Natural Products Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute Frederick Maryland 21702-1201 USA [email protected].
Abstract
A cell viability screen was conducted to identify natural products whose cytotoxicity depends on the presence or absence of topoisomerase 3β (TOP3B), the only known mammalian topoisomerase with the ability to resolve both DNA and RNA topological structures. Bioassay-guided fractionation of the organic solvent extract of Datura wrightii resulted in the identification of 11 new sesquiterpene lactones, including two germacranolides (1 and 2), eight heliangolides (3-10), and an eudesmanolide (11), along with nine known sesquiterpene lactones (12-20) belonging to the eudesmanolide, germacranolide, and guaianolide classes. The structures of the new compounds were elucidated by analysis of 1D and 2D NMR spectroscopic data and high-resolution mass spectrometric data. Their absolute configurations were determined based on a combination of modified Mosher's method, ECD simulation, and X-ray diffraction experiments. The new compound 10 exhibited moderate cytotoxic activity against both TOP3B-KO and TOP3B-WT cell lines, with EC50 values in the low micromolar range.
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BibTeX
@article{hwang2026daturolides,
title = {{Daturolides A-K, cytotoxic sesquiterpene lactones from Datura wrightii.}},
author = {Ji-Yeon Hwang and Brice A P Wilson and Lindsay Marron and Shar-Yin Naomi Huang and Ekaterina I Goncharova and Dongdong Wang and Yves Pommier and Barry R O'Keefe and Lin Du},
journal = {RSC advances},
year = {2026},
month = oct,
doi = {10.1039/d6ra08123a},
url = {https://europepmc.org/article/MED/42904217},
note = {CC BY},
}
RIS
TY - JOUR
TI - Daturolides A-K, cytotoxic sesquiterpene lactones from Datura wrightii.
AU - Ji-Yeon Hwang
AU - Brice A P Wilson
AU - Lindsay Marron
AU - Shar-Yin Naomi Huang
AU - Ekaterina I Goncharova
AU - Dongdong Wang
AU - Yves Pommier
AU - Barry R O'Keefe
AU - Lin Du
PY - 2026
DA - 2026/10/20
JO - RSC advances
DO - 10.1039/d6ra08123a
UR - https://europepmc.org/article/MED/42904217
AB - A cell viability screen was conducted to identify natural products whose cytotoxicity depends on the presence or absence of topoisomerase 3β (TOP3B), the only known mammalian topoisomerase with the ability to resolve both DNA and RNA topological structures. Bioassay-guided fractionation of the organic solvent extract of Datura wrightii resulted in the identification of 11 new sesquiterpene lactones, including two germacranolides (1 and 2), eight heliangolides (3-10), and an eudesmanolide (11), along with nine known sesquiterpene lactones (12-20) belonging to the eudesmanolide, germacranolide, and guaianolide classes. The structures of the new compounds were elucidated by analysis of 1D and 2D NMR spectroscopic data and high-resolution mass spectrometric data. Their absolute configurations were determined based on a combination of modified Mosher's method, ECD simulation, and X-ray diffraction experiments. The new compound 10 exhibited moderate cytotoxic activity against both TOP3B-KO and TOP3B-WT cell lines, with EC50 values in the low micromolar range.
SN - 2046-2069
ER -