Identification of Antifungal Compounds from Piper Plants Against Fusarium oxysporum: An Untargeted Metabolite Profiling-Based Approach

The phytopathogen Fusarium oxysporum produces considerable losses in economically important crops, making alternative control measures urgently required. Piper plants are widely distributed in tropical regions, and they are also known to produce metabolites with biological activity against infectious agents. As part of our continuous search for antifungals, 18 Piper-derived ethanolic extracts were evaluated by their in vitro effect on F oxysporum mycelial growth inhibition. The total content of phenol and flavonoid measurements and liquid chromatography-electrospray ionization-mass spectrometry analysis served as the chemical characterization of the investigated extracts. Piper pulchrum, Piper barcoense, and Piper tuberculatum exhibited the highest mycelial growth inhibition (>74%). The integration of chemical fingerprints and bioactivity datasets led to recognizing 4 bioactive candidates among extracts through single-Y orthogonal partial least squares regression and univariate statistics. These candidates were 2 amides (1,3), an alkyl lactone (2), and a prenylated benzoquinone (4), subsequently isolated and identified by nuclear magnetic resonance spectroscopy. These isolated compounds exhibited reasonable antifungal activity (IC50 < 50 mu M). The findings indicated that the correlative association is advantageous for identifying bioactive metabolites within active extracts.