Cytotoxic alkaloids from the root of <i>Zanthoxylum paracanthum</i> (mildbr) Kokwaro
Leonidah Kerubo Omosa, Vaderament‐A. Nchiozem‐Ngnitedem, Justus Mukavi, Brenda Atieno Okoko, Helder Ombui Nyaboke, H. Ibrahim, Jackson Obegi Matundura, Thomas Efferth, Michael Spiteller
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).