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

被引:27
作者
Letis, Antonios S. [1 ]
Seo, Ean-Jeong [2 ]
Nikolaropoulos, Sotiris S. [1 ]
Efferth, Thomas [2 ]
Giannis, Athanassios [3 ]
Fousteris, Manolis A. [1 ]
机构
[1] Univ Patras, Dept Pharm, Lab Med Chem, GR-26500 Patras, Greece
[2] Johannes Gutenberg Univ Mainz, Inst Pharm & Biochem, Dept Pharmaceut Biol, Staudinger Weg 5, D-55128 Mainz, Germany
[3] Univ Leipzig, Inst Organ Chem, Fac Chem & Mineral, Johannisallee 29, D-04103 Leipzig, Germany
关键词
Artemisinin; Cholic acid; Artemisin-derived hybrid; Leukemia; Anticancer activity; ANTIMALARIAL ACTIVITY; IN-VIVO; PLASMODIUM-FALCIPARUM; BIOLOGICAL EVALUATION; HUMAN CYTOMEGALOVIRUS; SIGNALING PATHWAYS; ACID DERIVATIVES; LUNG-CANCER; ARTESUNATE; DIHYDROARTEMISININ;
D O I
10.1016/j.bmc.2017.04.021
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 M-0.192 M against CCRF-CEM cells and between 0.345 JAM and 7.159 M 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 mu M and 0.345 +/- 0.031 mu M, 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. (C) 2017 Elsevier Ltd. All rights reserved.
引用
收藏
页码:3357 / 3367
页数:11
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