2. Academic Validation
  3. The Cytotoxic Cardiac Glycoside (-)-Cryptanoside A from the Stems of Cryptolepis dubia and Its Molecular Targets

The Cytotoxic Cardiac Glycoside (-)-Cryptanoside A from the Stems of Cryptolepis dubia and Its Molecular Targets

  • J Nat Prod. 2023 Jun 23;86(6):1411-1419. doi: 10.1021/acs.jnatprod.3c00094.
Yulin Ren 1,  Elizabeth N Kaweesa 2,  Lei Tian 3,  Sijin Wu 4,  Kongmany Sydara 5,  Mouachanh Xayvue 5,  Curtis E Moore 6,  Djaja D Soejarto 2 7,  Xiaolin Cheng 1,  Jianhua Yu 3,  Joanna E Burdette 2,  A Douglas Kinghorn 1
Affiliations

Affiliations

  • 1 Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, United States.
  • 2 Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, United States.
  • 3 City of Hope National Medical Center, Duarte, California 91010, United States.
  • 4 Shenzhen Jingtai Technology Co., Shenzhen 518000, Guangdong Province, People's Republic of China.
  • 5 Institute of Traditional Medicine, Ministry of Health, Vientiane XJ68+V3P, Lao People's Democratic Republic.
  • 6 X-ray Crystallography Facility, Department of Chemistry and Biochemistry, College of Arts and Sciences, The Ohio State University, Columbus, Ohio 43210, United States.
  • 7 Science and Education, Field Museum of Natural History, Chicago, Illinois 60605, United States.
PMID: 37216676 DOI: 10.1021/acs.jnatprod.3c00094
Abstract

A cardiac glycoside epoxide, (-)-cryptanoside A (1), was isolated from the stems of Cryptolepis dubia collected in Laos, for which the complete structure was confirmed by analysis of its spectroscopic and single-crystal X-ray diffraction data, using copper radiation at a low temperature. This cardiac glycoside epoxide exhibited potent cytotoxicity against several human Cancer cell lines tested, including HT-29 colon, MDA-MB-231 breast, OVCAR3 and OVCAR5 ovarian Cancer, and MDA-MB-435 melanoma cells, with the IC50 values found to be in the range 0.1-0.5 μM, which is comparable with that observed for digoxin. However, it exhibited less potent activity (IC50 1.1 μM) against FT194 benign/nonmalignant human fallopian tube secretory epithelial cells when compared with digoxin (IC50 0.16 μM), indicating its more selective activity toward human Cancer versus benign/nonmalignant cells. (-)-Cryptanoside A (1) also inhibited Na+/K+-ATPase activity and increased the expression of Akt and the p65 subunit of NF-κB but did not show any effects on the expression of PI3K. A molecular docking profile showed that (-)-cryptanoside A (1) binds to Na+/K+-ATPase, and thus 1 may directly target Na+/K+-ATPase to mediate its Cancer cell cytotoxicity.

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