Artemisinin-indole and artemisinin-imidazole hybrids: Synthesis, cytotoxic evaluation and reversal effects on multidrug resistance in MCF-7/ADR cells

Bioorg Med Chem Lett. 2019 May 1;29(9):1138-1142. doi: 10.1016/j.bmcl.2019.02.021. Epub 2019 Feb 20.

Abstract

A series of artemisinin derivatives with MDR reversal activity were designed and synthesized. All hybrids were screened to anticancer activities against four human cancer cell lines (A549, MCF-7, HepG-2, MDA-MB-231) and normal human hepatic cell (L02) in vitro. Most of the new compounds showed higher anticancer activities than artemisinin, among which compounds 11a and 11c displayed superior potency with IC50 6.78 μM and 5.25 μM against MCF-7, respectively. The further research indicated that the most potent 11c induced cell cycle arrest at G2 phase in MCF-7. Additionally, compound 11c showed remarkable MDR reversal activity which reversed adriamycin against MCF-7/ADR cells with IC50 0.76 μM.

Keywords: Anticancer activities; Artemisinin; Imidazole; Indole; MDR reversal activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Artemisinins / chemical synthesis*
  • Artemisinins / pharmacology*
  • Cell Survival / drug effects*
  • Drug Design
  • Drug Resistance, Multiple*
  • Drug Resistance, Neoplasm
  • Humans
  • MCF-7 Cells
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Artemisinins