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    Pharmacognosy Communications
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    Pharmacognosy Communications
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    Original Article

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

    wadmin1By wadmin1January 1, 2020Updated:August 6, 2021No Comments2 Mins Read
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    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.

    Pharmacognosy Communications,2020,10,1,44-51.
    DOI:10.5530/pc.2020.1.8
    Published: January 2020
    Type: Original Article

    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.

    Key words: Anticancer, in vitro, in silico, p53 Pathway, Rutaceae, Zanthoxylum zanthoxyloides.

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    About Journal
    About Journal

    Pharmacognosy Communications [Phcog Commn.] is a quarterly journal published by Phcog.Net. It is a peer reviewed journal aiming to publish high quality original research articles, methods, techniques and evaluation reports, critical reviews, short communications, commentaries and editorials of all aspects of medicinal plant research. The journal is aimed at a broad readership, publishing articles on all aspects of pharmacognosy, and related fields. The journal aims to increase understanding of pharmacognosy as well as to direct and foster further research through the dissemination of scientific information by the publication of manuscripts. The submission of original contributions in all areas of pharmacognosy are welcome.
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