Structure–Activity Relationship Analysis of Bufadienolide-Induced in Vitro Growth Inhibitory Effects on Mouse and Human Cancer Cells

The in vitro growth inhibitory effects of 27 bufadienolides and eight degradation products, with two cardenolides (ouabain and digoxin) chosen as reference compounds, were analyzed by means of an MTT colorimetric assay in six human and two mouse cancer cell lines. A structure–activity analysis was t...

Full description

Saved in:
Bibliographic Details
Published inJournal of natural products (Washington, D.C.) Vol. 76; no. 6; pp. 1078 - 1084
Main Authors Moreno Y. Banuls, Laetitia, Urban, Ernst, Gelbcke, Michel, Dufrasne, François, Kopp, Brigitte, Kiss, Robert, Zehl, Martin
Format Journal Article
LanguageEnglish
Published WASHINGTON American Chemical Society and American Society of Pharmacognosy 28.06.2013
Amer Chemical Soc
Subjects
Animals
Bufanolides - chemistry
Bufanolides - pharmacology
Chemistry, Medicinal
Drug Screening Assays, Antitumor
Humans
Life Sciences & Biomedicine
Mice
Molecular Structure
Pharmacology & Pharmacy
Plant Sciences
Science & Technology
Sodium-Potassium-Exchanging ATPase - genetics
Sodium-Potassium-Exchanging ATPase - metabolism
Structure-Activity Relationship
ALPHA-SUBUNITS
DRUG
SODIUM-PUMP
CYTOTOXIC BUFADIENOLIDES
NA+/K+-ATPASE
CHAN-SU
CARDIOTONIC STEROIDS
IDENTIFICATION
DES ARENOBUFAGINS
CARDIAC-GLYCOSIDES
Online AccessGet full text

Cover

More Information
Summary:The in vitro growth inhibitory effects of 27 bufadienolides and eight degradation products, with two cardenolides (ouabain and digoxin) chosen as reference compounds, were analyzed by means of an MTT colorimetric assay in six human and two mouse cancer cell lines. A structure–activity analysis was then performed to highlight the most important substituents relating to the in vitro growth inhibitory activity of bufadienolides in cancer cells. Thus, the current study revealed that various bufadienolides, including gamabufotalin rhamnoside (1a), bufotalin (2a), and hellebrin (3a), displayed higher growth inhibitory activities for various human cancer cell lines when compared to ouabain and digoxin. Gamabufotalin rhamnoside (1a) was the only compound that displayed growth inhibitory effects of <1 μM in mouse cancer cells that expressed mutated forms of the Na+,K+-ATPase α-1 subunit. In addition, all genins and degradation products displayed weaker (if any) in vitro growth inhibitory effects on cancer cells when compared to their respective glycosylated homologue, with the exception of hellebrigenin (3b), which was as active as hellebrin (3a).
ISSN:0163-3864
1520-6025
DOI:10.1021/np400034d