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- Title
Synthesis and Anticancer Cytotoxicity of Azaaurones Overcoming Multidrug Resistance.
- Authors
Tóth, Szilárd; Szepesi, Áron; Tran-Nguyen, Viet-Khoa; Sarkadi, Balázs; Német, Katalin; Falson, Pierre; Di Pietro, Attilio; Szakács, Gergely; Boumendjel, Ahcène
- Abstract
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.
- Subjects
MULTIDRUG resistance; P-glycoprotein; ATP-binding cassette transporters; STRUCTURE-activity relationships; ANTINEOPLASTIC agents; CANCER cells
- Publication
Molecules, 2020, Vol 25, Issue 3, p764
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules25030764