Cytotoxicity of fagaramide derivative and canthin-6-one from Zanthoxylum (Rutaceae) species against multidrug resistant leukemia cells

被引:21
作者
Omosa, Leonidah Kerubo [1 ]
Mbogo, Gacheru Martin [1 ]
Korir, Eric [1 ]
Omole, Ruth [4 ]
Seo, Ean-Jeong [2 ]
Yenesew, Abiy [1 ]
Heydenreich, Matthias [3 ]
Midiwo, Jacob Ogweno [1 ]
Efferth, Thomas [2 ]
机构
[1] Univ Nairobi, Dept Chem, Nairobi, Kenya
[2] Johannes Gutenberg Univ Mainz, Inst Pharm & Biochem, Dept Pharmaceut Biol, Mainz, Germany
[3] Univ Potsdam, Inst Chem, Potsdam, Germany
[4] Tech Univ Kenya, Dept Chem Sci & Technol, Nairobi, Kenya
关键词
Cytotoxicity; 4-(isoprenyloxy)-3-methoxy-3; 4-deoxymethylenedioxyfagaramide (1); canthin-6-one (3); multi-drug resistant leukemia cells; selectivity; Zanthoxylum chalybeum; Rutaceae;
D O I
10.1080/14786419.2019.1587424
中图分类号
O69 [应用化学];
学科分类号
081704 ;
摘要
In our continuous search for cytotoxic compounds from the genus Zanthoxylum, chromatographic separation of the MeOH/CH2Cl2 (1:1) extract of Z. chalybeum yielded one new alkamide; 4-(isoprenyloxy)-3-methoxy-3,4-deoxymethylenedioxyfagaramide (1) and a known one; fagaramide (2). Similarly, from the MeOH/CH2Cl2 (1:1) extract of the stem bark of Z. parachanthum four known compounds; canthin-6-one (3), dihydrochelerythrine (4), lupeol (5) and sesamin (6) were isolated. Characterization of the structures of these compounds was achieved using spectroscopic techniques (NMR and MS). Using resazurin reduction assay 1, 3 and 6 displayed moderate cytotoxicity with IC50 values below 50 mu M against the drug sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 leukemia cell lines. It is interesting to note that 3 was more active than the standard drug, doxorubicin against CEM/ADR5000 leukemia cells. Compounds 3 and 6 showed good selectivity on leukemia cells than normal cells. In future studies 3 should be tested against a panel of drug resistant human cells.
引用
收藏
页码:579 / 586
页数:8
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