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

Publication date: Available online 20 April 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Antonios S. Letis, Ean-Jeong Seo, Sotiris S. Nikolaropoulos, Thomas Efferth, Athanassios Giannis, Manolis A. Fousteris
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 0.019 µM to 0.192 µM against CCRF-CEM cells and between 0.345 µM and 7.159 µM 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 ± 0.001 µM and 0.345 ± 0.031 µM, 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.

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