1241906-85-3Relevant academic research and scientific papers
Synthesis and anticancer cytotoxicity of azaaurones overcoming multidrug resistance
Tóth, Szilárd,Szepesi, áron,Tran-Nguyen, Viet-Khoa,Sarkadi, Balázs,Német, Katalin,Falson, Pierre,Di Pietro, Attilio,Szakács, Gergely,Boumendjel, Ahcène
supporting information, (2020/02/18)
The resistance of tumors against anticancer drugs is a major impediment for chemotherapy. Tumors often develop multidrug resistance as a result of the cellular efflux of chemotherapeutic agents by ABC transporters such as P-glycoprotein (ABCB1/P-gp), Multidrug Resistance Protein 1 (ABCC1/MRP1), or Breast Cancer Resistance Protein (ABCG2/BCRP). By screening a chemolibrary comprising 140 compounds, we identified a set of naturally occurring aurones inducing higher cytotoxicity against P-gp-overexpressing multidrug-resistant (MDR) cells versus sensitive (parental, non-P-gp-overexpressing) cells. Follow-up studies conducted with the P-gp inhibitor tariquidar indicated that the MDR-selective toxicity of azaaurones is not mediated by P-gp. Azaaurone analogs possessing pronounced effects were then designed and synthesized. The knowledge gained from structure–activity relationships will pave the way for the design of a new class of anticancer drugs selectively targeting multidrug-resistant cancer cells.
1-Azaaurones derived from the naturally occurring aurones as potential antimalarial drugs
Souard, Florence,Okombi, Sabrina,Beney, Chantal,Chevalley, Severine,Valentin, Alexis,Boumendjel, Ahcne
scheme or table, p. 5724 - 5731 (2010/09/09)
We report the synthesis and in vitro antiplasmodial activity of 35 compounds, designed as analogues of the naturally occurring aurones. Several of these analogues showed submicromolar antimalarial activity against a chloroquine-resistant strain of Plasmodium falciparum (FcB1-Columbia strain) cultured on human erythrocytes. Substitution of the intracyclic oxygen in aurones by a nitrogen atom and systematic variation of the substituent at the B-ring revealed promising leads showing good activity on the CQ-resistant strain. In particular, 4,6-dimethoxy-4′-ethylazaaurone 22 showed antiplasmodial potency without noticeable toxicity. The easy synthesis of this family of compounds and the relevant antiplasmodial activity are in favor of promising candidates for further development.
