Unraveling Potential Bioactive Antimycobacterial Compounds from Endophytic Aspergillus tubingensis and Syncephalastrum racemosum: An Integrated Bioassay, Metabolite Profiling, and Molecular Mechanism Approach
DOI:
https://doi.org/10.48048/tis.2026.12071Keywords:
Antimycobacterial, Aspergillus tubingensis, Syncephalastrum racemosum, Ethyl acetate extract, Harrisonia perforata, Molecular docking, Mass Spectrometry, Antimycobacterial, Aspergillus tubingensis, Syncephalastrum racemosum, Ethyl acetate extract, Harrisonia perforata, Molecular docking, Mass SpectrometryAbstract
Tuberculosis (TB), a significant global health threat, ranks third in the world, with 67% of cases occurring in productive age groups. Natural compounds, such as fungal secondary metabolites, exhibit various pharmaceutically relevant activities, including antimycobacterial activity. Our ongoing research investigated the ethyl acetate extract of endophytic fungi Aspergillus tubingensis and Syncephalastrum racemosum from Rui (Harrisonia perforata) against Mycobacterium tuberculosis. The extract was obtained by fermenting the fungi on PDB and extracting the liquid culture using ethyl acetate. It showed antimycobacterial activity against Mycobacterium tuberculosis H37Rv by culturing the crude extract and bacteria in Middlebrook 7H9 Broth and Middlebrook 7H10 Agar. UHPLC-MS/MS profiling revealed about 85 compounds from Aspergillus tubingensis and 105 from Syncephalastrum racemosum. Molecular docking analysis revealed potential dual-action mechanisms by targeting two crucial enzymes in M. tuberculosis: KatG and KasA. Potential metabolites include bis(methylbenzylidene)sorbitol, sphinganine, and a chromenone derivative. In conclusion, the crude extract of Aspergillus tubingensis and Syncephalastrum racemosum demonstrates potential as an antimycobacterial agent.
HIGHLIGHTS
Our study focuses on an ethyl acetate extract of endophytic fungi Aspergillus tubingensis and Syncephalastrum racemosum isolated from Harrisonia perforata collected from Palu, Central Sulawesi, Indonesia. Endophytic fungi produce secondary metabolites with various pharmacological activities, including antibacterial activity. Tuberculosis (TB) remains a significant health problem, especially in Asia and Indonesia. The current TB medicine has become resistant to Mycobacterium tuberculosis, the leading cause of the disease. Therefore, finding new TB treatment agents is crucial. Our study aims to identify new agents for TB treatment and encourage scientists to explore endophytic fungi as potential sources. Our study is the first to profile the metabolites of Aspergillus tubingensis and Syncephalastrum racemosum for treating Mycobacterium. We conducted fungi fermentation and performed HPLC-HRMS to profile the metabolites. In vitro bioassays examined their activity, and molecular docking analyzed their molecular mechanisms.
GRAPHICAL ABSTRACT
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