Nonprenylated rotenoids, a new class of potent breast cancer resistance protein inhibitors.

Abstract

Two rotenoids isolated from Boerhaavia diffusa (Nyctaginaceae), boeravinones G (1) and H (2), have been found to potently inhibit the drug efflux activity of breast cancer resistance protein (BCRP/ABCG2), a multidrug transporter responsible for cancer cell resistance to chemotherapy. The isolation of nine additional rotenoid derivatives (3-11), including the new boeravinones I (10) and J (11), from the extract of B. diffusa roots allowed us to establish structure-activity relationships toward inhibition of BCRP-mediated drug transport activity. The results show the positive roles of a methoxy group at position 6 of ring B and the absence of a substituent at position 10, and the requirement for a 6a/12a double bond between rings B and C. In contrast, both contraction of ring B, to give a coumaronochromone (11), and tetrasubstitution of ring D appeared to be detrimental for the inhibitory potency. The present study provides the first data on the BCRP-inhibiting activity of rotenoid derivatives, indicating boeravinones as a new class of interesting BCRP inhibitors.

• Authors: Abdelhakim Ahmed-Belkacem, Sira Macalou, Francesca Borrelli, Raffaele Capasso, Ernesto Fattorusso, Orazio Taglialatela-Scafati, Attilio Di Pietro
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 50 Issue 8 Pg. 1933-8 (Apr 19 2007) ISSN: 0022-2623 [Print] United States
• PMID: 17341062 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ABCG2 protein, human
• ATP Binding Cassette Transporter, Subfamily G, Member 2
• ATP-Binding Cassette Transporters
• Isoflavones
• Neoplasm Proteins
• Plant Extracts

Topics

• ATP Binding Cassette Transporter, Subfamily G, Member 2
• ATP-Binding Cassette Transporters (antagonists & inhibitors)
• Cell Line
• Drug Resistance, Multiple
• Drug Resistance, Neoplasm
• Humans
• Isoflavones (chemistry, isolation & purification, pharmacology)
• Neoplasm Proteins (antagonists & inhibitors)
• Nyctaginaceae (chemistry)
• Plant Extracts (chemistry, isolation & purification)
• Structure-Activity Relationship