TY - JOUR
T1 - Antitumor agents. 280. Multidrug resistance-selective desmosdumotin B analogues
AU - Nakagawa-Goto, Kyoko
AU - Chang, Po Cheng
AU - Lai, Chin Yu
AU - Hung, Hsin Yi
AU - Chen, Tzu Hsuan
AU - Wu, Pei Chi
AU - Zhu, Hao
AU - Sedykh, Alexander
AU - Bastow, Kenneth F.
AU - Lee, Kuo Hsiung
PY - 2010/9/23
Y1 - 2010/9/23
N2 - 6,6,8-Triethyldesmosdumotin B (2) was discovered as a MDR-selective flavonoid with significant in vitro anticancer activity against a multidrug resistant (MDR) cell line (KB-VIN) but without activity against the parent cells (KB). Additional 2 analogues were synthesized and evaluated to determine the effect of B-ring modifications on MDR-selectivity. Analogues with a B-ring Me (3) or Et (4) group had substantially increased MDR selectivity. Three new disubstituted analogues, 35, 37, and 49, also had high collateral sensitivity (CS) indices of 273, 250, and 100, respectively. Furthermore, 2-4 also displayed MDR selectivity in an MDR hepatoma-cell system. While 2-4 showed either no or very weak inhibition of cellular P-glycoprotein (P-gp) activity, they either activated or inhibited the actions of the first generation P-gp inhibitors verapamil or cyclosporin, respectively.
AB - 6,6,8-Triethyldesmosdumotin B (2) was discovered as a MDR-selective flavonoid with significant in vitro anticancer activity against a multidrug resistant (MDR) cell line (KB-VIN) but without activity against the parent cells (KB). Additional 2 analogues were synthesized and evaluated to determine the effect of B-ring modifications on MDR-selectivity. Analogues with a B-ring Me (3) or Et (4) group had substantially increased MDR selectivity. Three new disubstituted analogues, 35, 37, and 49, also had high collateral sensitivity (CS) indices of 273, 250, and 100, respectively. Furthermore, 2-4 also displayed MDR selectivity in an MDR hepatoma-cell system. While 2-4 showed either no or very weak inhibition of cellular P-glycoprotein (P-gp) activity, they either activated or inhibited the actions of the first generation P-gp inhibitors verapamil or cyclosporin, respectively.
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U2 - 10.1021/jm100846r
DO - 10.1021/jm100846r
M3 - Article
C2 - 20735140
AN - SCOPUS:77956785606
VL - 53
SP - 6699
EP - 6705
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 18
ER -