TY - JOUR
T1 - Nonprenylated rotenoids, a new class of potent breast cancer resistance protein inhibitors
AU - Ahmed-Belkacem, Abdelhakim
AU - Macalou, Sira
AU - Borrelli, Francesca
AU - Capasso, Raffaele
AU - Fattorusso, Ernesto
AU - Taglialatela-Scafati, Orazio
AU - Di Pietro, Attilio
PY - 2007/4/19
Y1 - 2007/4/19
N2 - 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.
AB - 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.
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U2 - 10.1021/jm061450q
DO - 10.1021/jm061450q
M3 - Article
C2 - 17341062
AN - SCOPUS:34247225559
SN - 0022-2623
VL - 50
SP - 1933
EP - 1938
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 8
ER -