Cytotoxic alkaloids from the root of Zanthoxylum paracanthum (mildbr) Kokwaro

Abstract

Chemical investigation of the root of Zanthoxylum paracanthum afforded 1 new alkamide derivative, (2E,4E)-6-oxo-N-isobutyldeca-2,4-dienamide (1) together with 10 known congeners including one phenolic amide (2), four benzophenanthridines (3 − 6), three indolonaphthyridines (7 − 9) and two lignans (10 and 11). Their structures were elucidated by a combination of spectroscopic and spectrometric data. Using resazurin reduction assay, the crude extract (10 µg/mL) and isolates (10 µM) were screened for their cytotoxic activities against the drug-sensitive (CCRF-CEM) leukemia cell line and its multidrug-resistant counterpart (CEM/ADR5000). Compounds 3, 4 and 6 showed cytotoxicity against CCRF-CEM with IC₅₀ values of 2.00 ± 0.33, 2.31 ± 0.20 and 0.11 ± 0.04 µM, respectively. Only compound 6 exhibited strong cytotoxic activity against CEM/ADR5000 with an IC₅₀ value of 2.34 ± 0.34 µM in comparison with the standard drug doxorubicin which showed IC₅₀ values of 0.01 ± 0.14 (CCRF-CEM) and 26.78 ± 3.30 µM (CEM/ADR5000).

Graphical Abstract

Keywords:

• Zanthoxylum paracanthum
• Rutaceae
• alkamide
• cytotoxicity

Acknowledgements

Special thanks to Mr. Patrick Mutiso of the Herbarium, School of Biological Science, University of Nairobi for authentication of the plant material. We are also thankful to Dr. Wolf Hiller (Faculty of Chemistry and Chemical Biology, TU Dortmund) for NMR analysis, Drs. K.G. Bedane and G.T.M. Bitchagno for valuable discussions. Special thank go to Mrs. Eva Maria Wieczorek (INFU, TU Dortmund) for acquisitions of HRESIMS.

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

L. K. Omosa is grateful for the financial support from the International Science Program (ISP) Sweden, through the KEN-02 project.