Molecular networking-based mass spectral identification of Brucea javanica (L.) Merr. metabolites and their selective binding affinities for dengue virus enzymes

Nor Syaidatul Akmal Mohd Yousof; Adlin Afzan; Murizal Zainol; Syahrul Imran Abu Bakar; Mohd Ridzuan Mohd Abd Razak; Nur Hana Md Jelas; Nor Nadirah Abdullah; Geoffrey A Cordell; Nor Hadiani Ismail

doi:10.1016/j.fitote.2024.105955

Molecular networking-based mass spectral identification of Brucea javanica (L.) Merr. metabolites and their selective binding affinities for dengue virus enzymes

Fitoterapia. 2024 Apr 9:175:105955. doi: 10.1016/j.fitote.2024.105955. Online ahead of print.

Authors

Nor Syaidatul Akmal Mohd Yousof¹, Adlin Afzan², Murizal Zainol², Syahrul Imran Abu Bakar³, Mohd Ridzuan Mohd Abd Razak², Nur Hana Md Jelas², Nor Nadirah Abdullah³, Geoffrey A Cordell⁴, Nor Hadiani Ismail⁵

Affiliations

¹ Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia; Faculty of Applied Science, UiTM, 40450 Shah Alam, Selangor, Malaysia; Herbal Medicine Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health, No. 1 Jalan Setia Murni U13/52, Seksyen U13, Setia Alam, 40170 Shah Alam, Selangor Darul Ehsan, Malaysia.
² Herbal Medicine Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health, No. 1 Jalan Setia Murni U13/52, Seksyen U13, Setia Alam, 40170 Shah Alam, Selangor Darul Ehsan, Malaysia.
³ Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia; Faculty of Applied Science, UiTM, 40450 Shah Alam, Selangor, Malaysia.
⁴ Natural Products Inc., Evanston, IL 60201, USA; College of Pharmacy, University of Florida, Gainesville, FL 32610, USA.
⁵ Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia; Faculty of Applied Science, UiTM, 40450 Shah Alam, Selangor, Malaysia. Electronic address: norhadiani@uitm.edu.my.

PMID: 38604259
DOI: 10.1016/j.fitote.2024.105955

Abstract

Brucea javanica, a valued traditional medicinal plant in Malaysia, known for its fever-treating properties yet remains underexplored for its potential antiviral properties against dengue. This study aims to simultaneously identify chemical classes and metabolites within B. javanica using molecular networking (MN), by Global Natural Product Social (GNPS), and SIRIUS in silico annotation. Liquid chromatography-mass spectrometry (LC-MS²⁾-based MN explores chemical diversity across four plant parts (leaves, roots, fruits, and stem bark), revealing diverse metabolites such as tryptophan-derived alkaloids, terpenoids, and octadecadenoids. Simultaneous LC-MS² and MN analyses reveal a discriminative capacity for individual plant components, with roots accumulating tryptophan alkaloids, fruits concentrating quassinoids, leaves containing fusidanes, and stem bark primarily characterised by simple indoles. Subsequently, extracts were evaluated for dengue antiviral activity using adenosine triphosphate (ATP) and plaque assays, indicates potent efficacy in the dichloromethane (DCM) extract from roots (EC₅₀ = 0.3 μg/mL, SI = 10). Molecular docking analysis of two major compounds; canthin-6-one (264) and 1-hydroxy-11-methoxycanthin-6-one (275) showed potential binding interactions with active sites of NS5 RNA-dependent RNA polymerase (RdRp) of dengue virus (DENV) protein. Subsequent in vitro evaluation revealed compounds 264 and 275 had a promising dengue antiviral activity with SI value of 63 and 1.85. These identified metabolites emerge as potential candidates for further evaluation in dengue antiviral activities.

Keywords: Brucea javanica roots; Chemical classification; Dengue virus; Metabolite annotation; Molecular docking; Molecular networking.