1241906-91-1Relevant academic research and scientific papers
1-Azaaurones derived from the naturally occurring aurones as potential antimalarial drugs
Souard, Florence,Okombi, Sabrina,Beney, Chantal,Chevalley, Severine,Valentin, Alexis,Boumendjel, Ahcne
, p. 5724 - 5731 (2010)
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.
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.
