Design, synthesis, and biological evaluation of artemisinin-indoloquinoline hybrids as potent antiproliferative agents

Molecules. 2014 Nov 18;19(11):19021-35. doi: 10.3390/molecules191119021.


A series of artemisinin-indoloquinoline hybrids were designed and synthesized in an attempt to develop potent and selective anti-tumor agents. Compounds 7a-7f, 8 and 9 were prepared and characterized. Their antiproliferative activities against MV4-11, HCT-116, A549, and BALB/3T3 cell lines in vitro were tested. Nearly all of the tested compounds (7-9, except for compounds 7d and 7e against HCT-116) showed an increased antitumor activity against HCT-116 and A549 cell lines when compared to the dihydroartemisinin control. Especially for the artemisinin-indoloquinoline hybrid 8, with an 11-aminopropylamino-10H-indolo[3,2-b]quinoline substituent, the antiproliferative activity against the A549 cell line had improved more than ten times. The IC50 value of hybrid 8 against A549 cell lines was decreased to 1.328 ± 0.586 μM, while dihydroartemisin showed IC50 value of >20 µM in the same cell line. Thus, these results have proven that the strategy of introducing a planar basic fused aromatic moiety, such as the indoloquinoline skeleton, could improve the antiproliferative activity and selectivity towards cancer cell lines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology*
  • Artemisinins / chemical synthesis*
  • Artemisinins / pharmacology*
  • BALB 3T3 Cells
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Drug Screening Assays, Antitumor / methods
  • HCT116 Cells
  • Humans
  • Mice
  • Quinolines / chemical synthesis*
  • Quinolines / pharmacology*
  • Structure-Activity Relationship


  • Antineoplastic Agents
  • Artemisinins
  • Quinolines
  • artenimol
  • artemisinin
  • quinoline