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

Abstract

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 μM 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.

Graphical Abstract

Keywords:

• Cytotoxicity
• 4-(isoprenyloxy)-3-methoxy-3,4-deoxymethylenedioxyfagaramide (1)
• canthin-6-one (3)
• multi-drug resistant leukemia cells
• selectivity
• Zanthoxylum chalybeum
• Rutaceae

Acknowledgement

The authors would like to thank the International Science Programme, Uppsala University, Sweden (ISP) through the KEN-02 project for providing funds for reagents for the isolation process. The authors wish to thank Mr. Patrick Chalo Mutiso for the identification and collection of the plant materials from which the compounds were isolated.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

Funds for this work was provided by the International Science Programme, Uppsala University, Sweden (ISP) through the KEN-02 project.