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

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 mu g/mL) and isolates (10 mu M) 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 mu M, respectively. Only compound 6 exhibited strong cytotoxic activity against CEM/ADR5000 with an IC50 value of 2.34 +/- 0.34 mu M in comparison with the standard drug doxorubicin which showed IC50 values of 0.01 +/- 0.14 (CCRF-CEM) and 26.78 +/- 3.30 mu M (CEM/ADR5000).

Automated summary

Chemical investigation of Zanthoxylum paracanthum root led to the discovery of a new alkamide derivative and 10 known compounds with cytotoxic activities against leukemia cell lines. Compound 6 showed strong cytotoxic activity against the multidrug-resistant leukemia cell line.