Erythrofordins D and E, two new cassaine-type diterpenes from Erythrophleum suaveolens.

Abstract

Two new cassaine-type diterpenoids, namely erythrofordins D (1) and E (2), sourced from a Cameroon collection of Erythrophleum suaveolens were isolated and assessed for anti-tumor activity. In the NCI-60 cancer cell assay, erythrofordins D (1) and E (2) were found to be cytotoxic in the low micro molar ranges with a mean GI50 value of 2.45 and 0.71 µM, mean TGI value of 9.77 and 2.29 µM, and a mean LC50 of 26.92 and 11.48 µM for 1 and 2 respectively. Using the COMPARE algorithm, the new compounds were found to have similar NCI-60 response profiles to the known cardiac glycosides hyrcanoside and strophanthin. In addition, in an assay examining the viability and contractile function in human cardiomyocytes derived from induced pluripotent stem-cells, erythrofordins showed cardiotoxicity effects at concentrations as low as 0.03 µg/mL.

• Authors: Tanja Grkovic, Jason R Evans, Rhone K Akee, Liang Guo, Myrtle Davis, Johnson Jato, Paul G Grothaus, Michelle Ahalt-Gottholm, Melinda Hollingshead, Jerry M Collins, David J Newman, Barry R O'Keefe
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 29 Issue 2 Pg. 134-137 (01 15 2019) ISSN: 1464-3405 [Electronic] England
• PMID: 30553734 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)
• Copyright: Copyright © 2018 Elsevier Ltd. All rights reserved.

Chemical References

• Diterpenes

Topics

• Caesalpinia (chemistry)
• Cell Survival (drug effects)
• Diterpenes (chemistry, isolation & purification, pharmacology)
• Dose-Response Relationship, Drug
• Humans
• Molecular Structure
• Myocytes, Cardiac (drug effects)
• Structure-Activity Relationship