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.
Nonprenylated rotenoids, a new class of potent breast cancer resistance protein inhibitors / AHMED BELKACEM, A; Macalou, S; Borrelli, Francesca; Capasso, Raffaele; Fattorusso, Ernesto; TAGLIALATELA SCAFATI, Orazio; DI PIETRO, A.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - STAMPA. - 50:(2007), pp. 1933-1938. [10.1021/jm061450q]
Nonprenylated rotenoids, a new class of potent breast cancer resistance protein inhibitors
BORRELLI, FRANCESCA;CAPASSO, RAFFAELE;FATTORUSSO, ERNESTO;TAGLIALATELA SCAFATI, ORAZIO;
2007
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.File | Dimensione | Formato | |
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