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

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Abstract
Pharmacognosy Communications,2020,10,1,44-51.
Published:December 2019
Type:Original Article

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

Moses Andima1,2,*, Paolo Coghi3, Li Jun Yang4, Vincent Kam Wai Wong4, Chrispus Mutuku Ngule5,6, Matthias Heydenreich7, Albert Jairo Ndakala1, Abiy Yenesew1, Solomon Derese1

1Department of Chemistry, University of Nairobi, Chiromo Road, Nairobi, KENYA.

2Department of Chemistry, Busitema University, Tororo, UGANDA.

3School of Pharmacy, Bld. E, Macau University of Science and Technology, Avenida Wai Long, Macau, CHINA.

4State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Macau, CHINA.

5Kenya Medical Research Institute, Off Mbagathi Road, Nairobi, KENYA.

6Department of Chemistry, Youngstown State University, Ohio, USA.

7Institut für Chemie, Universität Potsdam, Karl-Liebknecht-Str, Potsdam, GERMANY.

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 zanthoxyloides and their probable in silico anticancer mechanisms of action. Methods: Column chromatography was used to isolate compounds from MeOH:CH2Cl2 (1:1) extract of the stem bark extract of Zanthoxylum zanthoxyloides. 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 (IC50 21.2), breast cancer (BT549) cells, (IC50 21.2 μM). Similarly, sesamin (4) exhibited moderate inhibitory activity against BT549 cancer cells (IC50 47.6 μM). Hesperidin (5) showed low inhibitory activity against A549 and HEp2 (Larynx) cells but was significantly toxic to normal liver and lung cells. In silico docking studies showed that all the compounds strongly bind to cyclin-dependent kinases (CDK2 and CDK6) and weakly bind to caspases 3 and 8 suggesting that they inhibit cancer cells by inducing cell cycle arrest and apoptosis. Conclusion: This study indicates that the compounds isolated from Z. zanthoxyloids hold promise as potential leads against cancer. Due to high toxicity of compound 5 against normal lung and liver cells, it deserves further toxicity investigations to access its safety before in vivo trials.

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