Planta Med 2023; 89(14): 1405
DOI: 10.1055/s-0043-1774209
Abstracts
Wednesday 5th July 2023 | Poster Session III
Molecular modelling/ Virtual screening/ Metabolomics/Molecular networking/ Chemometrics and profiling

Probing the Secondary Metabolites in Brucea javanica (L.) Merr. Root through Mass Spectroscopy with Molecular Networking for Dengue Antiviral Activity

Authors

  • Nor Mohd Yousof

    1   Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA, Bandar Puncak Alam, Malaysia
    2   Institute for Medical Research, National Health Institute, Setia Alam, Malaysia

  • Adlin Afzan

    2   Institute for Medical Research, National Health Institute, Setia Alam, Malaysia

  • Murizal Zainol

    2   Institute for Medical Research, National Health Institute, Setia Alam, Malaysia

  • Syahrul Abu Bakar

    1   Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA, Bandar Puncak Alam, Malaysia

  • Mohd Abd Razak

    2   Institute for Medical Research, National Health Institute, Setia Alam, Malaysia

  • Nor Hadiani Ismail

    1   Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA, Bandar Puncak Alam, Malaysia
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    Bruea javanica (L.) Merr. is a medicinal plant used traditionally for fever treatment in Malaysia. The dichloromethane roots extract was found to have good dengue antiviral activity with EC50=0.3±0.08 µg/mL and CC50=2.99±0.99 µg/mL (SI of 9.96) in adenosine triphosphate (ATP) assay and plaque assay. With the aim of identifying the dengue antiviral compounds, a comprehensive analysis of the chemical space in the root extract of B. javanica using a combination of untargeted LC-MS2 and molecular networking analysis was undertaken. MS data pre-processing using MZmine3 revealed 254 MS features in positive and 237 in negative ionisation mode, forming three distinct but chemotaxonomically related clusters, which are carboline alkaloids, indole alkaloids and quassinoids. Seven compounds were isolated from the roots, which are canthin-6-one, canthin-6-one-N-oxide, methoxycantin-6-one, methoxy- hydroxycanthin-6-one, brusatol, bruceolline J and bruceolline E. Among them, canthin-6-one and canthin-6- one-N-oxide showed good binding energies (-17.8689 kcal/mol and -6.3425 kcal/mol, respectively) in molecular docking studies against DENV-2 NS5 RNA-dependent RNA polymerase (RdRp) protein. Both compounds also exhibited in vitro dengue antiviral activity, with canthin-6-one having an EC50 of 0.86 µM (SI =63), and canthin-6-one-N-oxide an EC50 of 1.6 µM (SI=46) in a plaque assay. These findings offer promising leads for further studies towards understanding the role of these natural products as dengue antivirals.


     

    Publication History

    Article published online:
    16 November 2023

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