2. Academic Validation
  3. Synthesis of nοvel artemisinin dimers with polyamine linkers and evaluation of their potential as anticancer agents

Synthesis of nοvel artemisinin dimers with polyamine linkers and evaluation of their potential as anticancer agents

  • Bioorg Med Chem. 2017 Jul 15;25(14):3756-3767. doi: 10.1016/j.bmc.2017.05.018.
George E Magoulas 1,  Tzoanna Tsigkou 2,  Lina Skondra 2,  Margarita Lamprou 2,  Panagiota Tsoukala 1,  Vassiliki Kokkinogouli 1,  Evangelia Pantazaka 2,  Dionissios Papaioannou 1,  Constantinos M Athanassopoulos 3,  Evangelia Papadimitriou 4
Affiliations

Affiliations

  • 1 Laboratory of Synthetic Organic Chemistry, Department of Chemistry, University of Patras, GR-26504 Patras, Greece.
  • 2 Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Patras, GR-26504 Patras, Greece.
  • 3 Laboratory of Synthetic Organic Chemistry, Department of Chemistry, University of Patras, GR-26504 Patras, Greece. Electronic address: kath@chemistry.upatras.gr.
  • 4 Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Patras, GR-26504 Patras, Greece. Electronic address: epapad@upatras.gr.
PMID: 28549888 DOI: 10.1016/j.bmc.2017.05.018
Abstract

The natural product artemisinin and derivatives thereof are currently considered as the drugs of choice for the treatment of malaria. At the same time, a significant number of such drugs have also shown interesting Anticancer activity. In the context of the present research work, artemisinin was structurally modified and anchored to naturally occurring polyamines to afford new artemisinin dimeric conjugates whose potential Anticancer activity was evaluated. All artemisinin conjugates tested were more effective than artemisinin itself in decreasing the number of MCF7 breast Cancer cells. The effect required conjugation and was not due to the artemisinin analogue or the polyamine, alone or in combination. To elucidate potential mechanism of action, we used the most effective conjugates 6, 7, 9 and 12 and found that they decreased expression and secretion of the angiogenic growth factor pleiotrophin by the Cancer cells themselves, and inhibited angiogenesis in vivo and endothelial cell growth in vitro. These data suggest that the new artemisinin dimers are good candidates for the development of effective Anticancer agents.

Keywords

Angiogenesis; Artemisinin; Breast cancer; Conjugates; Dimers; Endothelial cells; Polyamines.

Figures