1093400-52-2Relevant academic research and scientific papers
Synthesis of Resveratrol Derivatives and in Vitro Screening for Potential Cancer Chemopreventive Activities
Orsini, Fulvia,Verotta, Luisella,Klimo, Karin,Gerh?user, Clarissa
, p. 414 - 427 (2016)
New resveratrol (trans-3,4',5-trihydroxystilbene) analogs were synthesized and screened for their in vitro cancer chemopreventive potential using various bioassays relevant for the prevention of carcinogenesis in humans: two assays to detect modulators of
Methoxy stilbenes as potent, specific, untransported, and noncytotoxic inhibitors of breast cancer resistance protein
Valdameri, Glaucio,Pereira Rangel, Luciana,Spatafora, Carmela,Guitton, Jerome,Gauthier, Charlotte,Arnaud, Ophelie,Ferreira-Pereira, Antonio,Falson, Pierre,Winnischofer, Sheila M. B.,Rocha, Maria E. M.,Tringali, Corrado,Pietro, Attilio Di
experimental part, p. 322 - 330 (2012/07/27)
The ABCG2 multidrug transporter is known to confer cancer cell multidrug resistance by causing the efflux of anticancer drugs; therefore, selective inhibitors have the potential to improve chemotherapeutic treatments. Here, various methoxy derivatives of resveratrol are shown to be potent inhibitors of mitoxantrone efflux by ABCG2: among a series of 11 derivatives, compound 9 (3,5,3′,4′-tetramethoxy trans-stilbene) had an IC50 of 0.16 μM and showed a maximal inhibition of 75%, as measured by flow cytometry. It was not transported, as shown by HPLC fractionation and mass spectrometry titration and the lack of any cross-resistance in cell survival experiments. Compound 9 had a very low intrinsic cytotoxicity and was able to chemosensitize the growth of resistant ABCG2-transfected HEK293 cells at submicromolar concentrations. Drug-efflux inhibition was specific for ABCG2 since very low effects were observed with ABCB1 and ABCC1. The action mechanism of compound 9 was different from that of GF120918, which produced a complete and partly competitive but not ABCG2-specific inhibition, since ABCB1 was even more strongly inhibited. The two inhibitors also displayed different effects on the ABCG2 vanadate-sensitive ATPase activity, suggesting that they either bound to distinct sites or induced different conformational changes. Mitoxantrone efflux was fully inhibited by combining low concentrations of compound 9 with either GF120918 or a transport substrate such as prazosin or nilotinib. We conclude that methoxy derivatives of stilbene are good candidates for investigating future in vivo modulation of ABCG2 drug-efflux activity.
