Antiproliferative Activity of Secondary Metabolites from Zanthoxylum zanthoxyloides Lam: In vitro and in silico Studies

Abstract

Background: Plant derived compounds have provided proming leads in search for safer anticancer chemotherapies. Zanthoxylum zanthoxyloides is a common medicinal plant in Uganda whose bioactive composition has not been fully elucidated. The aim of this study was to evaluate the in vitro antiproliferative potential of compounds isolated from Zanthoxylum zan-thoxyloides and their probable in silico anticancer mechanisms of action. Methods: Column chromatography was used to isolate compounds from MeOH:CH 2 Cl 2 (1:1) extract of the stem bark extract of Zanthoxylum zan-thoxyloides. The structures of the isolated compounds were elucidated by NMR and MS analyses. MTT assay was used to measure cell viability. Using in silico docking, the interaction of the compounds with key target proteins in the p53 pathway was determined. Results: From the root bark of this plant five compounds were isolated, namely; dihydrochelerythrine (1), skimmianine (2), tridecan-2-one (3), sesamin (4) and hesperidin (5). Dihydrochelerythrine (1) inhibited proliferation of liver cancer (HCC) cells (IC 50 21.2), breast cancer (BT549) cells, (IC 50 21.2 μM). Similarly, sesamin (4) exhibited moderate inhibitory activity against BT549 cancer cells (IC 50 47.6 μM). Hesperidin (5) showed low inhibitory activity against A549 and HEp 2 (Larynx) cells but was significantly toxic to normal liver and lung cells.