Synthesis and anticancer cytotoxicity of azaaurones overcoming multidrug resistance

Szilárd Tóth, Áron Szepesi, Viet Khoa Tran-Nguyen, Balázs Sarkadi, Katalin Német, Pierre Falson, Attilio Di Pietro, Gergely Szakács, Ahcène Boumendjel

Research output: Contribution to journalArticle


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.

Original languageEnglish
Article number764
Issue number3
Publication statusPublished - Feb 10 2020



  • Anticancer
  • Aurone
  • Azaaurone
  • Cytotoxicity
  • Multidrug resistance
  • Overexpression
  • P-gp

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

Cite this

Tóth, S., Szepesi, Á., Tran-Nguyen, V. K., Sarkadi, B., Német, K., Falson, P., Di Pietro, A., Szakács, G., & Boumendjel, A. (2020). Synthesis and anticancer cytotoxicity of azaaurones overcoming multidrug resistance. Molecules, 25(3), [764].