2. Academic Validation
  3. Synthesis and cytotoxic activity of new artemisinin hybrid molecules against human leukemia cells

Synthesis and cytotoxic activity of new artemisinin hybrid molecules against human leukemia cells

  • Bioorg Med Chem. 2017 Jul 1;25(13):3357-3367. doi: 10.1016/j.bmc.2017.04.021.
Antonios S Letis 1,  Ean-Jeong Seo 2,  Sotiris S Nikolaropoulos 1,  Thomas Efferth 2,  Athanassios Giannis 3,  Manolis A Fousteris 4
Affiliations

Affiliations

  • 1 Laboratory of Medicinal Chemistry, Department of Pharmacy, University of Patras, Patras GR-26500, Greece.
  • 2 Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, 55128 Mainz, Germany.
  • 3 Institute of Organic Chemistry, Faculty of Chemistry and Mineralogy, University of Leipzig, Johannisallee 29, Leipzig 04103, Germany. Electronic address: giannis@uni-leipzig.de.
  • 4 Laboratory of Medicinal Chemistry, Department of Pharmacy, University of Patras, Patras GR-26500, Greece. Electronic address: manolisf@upatras.gr.
PMID: 28456567 DOI: 10.1016/j.bmc.2017.04.021
Abstract

A series of new artemisinin-derived hybrids which incorporate cholic acid moieties have been synthesized and evaluated for their antileukemic activity against sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 cells. The new hybrids 20-28 showed IC50 values in the range of 0.019µM-0.192µM against CCRF-CEM cells and between 0.345µM and 7.159µM against CEM/ADR5000 cells. Amide hybrid 25 proved the most active compound against both CCRF-CEM and CEM/ADR5000 cells with IC50 value of 0.019±0.001µM and 0.345±0.031µM, respectively. A relatively low cross resistance to hybrids 20-28 in the range of 5.7-fold to 46.1-fold was measured. CEM/ADR5000 cells showed higher resistance than CCRF-CEM to all the tested compounds. Interestingly, the lowest cross resistance to 23 was observed (5.7-fold), whereas hybrid 25 showed 18.2-fold cross-resistant to CEM/ADR5000 cells. Hybrid 25 which proved even more potent than clinically used doxorubicin against CEM/ADR5000 cells may serve as a promising antileukemic agent against both sensitive and multidrug-resistant cells.

Keywords

Anticancer activity; Artemisin-derived hybrid; Artemisinin; Cholic acid; Leukemia.

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