Bioactivity-Guided Metabolite Profiling of Feijoa (<i>Acca sellowiana</i>) Cultivars Identifies 4‑Cyclopentene-1,3-dione as a Potent Antifungal Inhibitor of Chitin Synthesis

Pathogenic fungi continue to develop resistance against current antifungal drugs. To explore the potential of agricultural waste products as a source of novel antifungal compounds, we obtained an unbiased GC-MS profile of 151 compounds from 16 commercial and experimental cultivars of feijoa peels. Multivariate analysis correlated 93% of the compound profiles with antifungal bioactivities. Of the 18 compounds that significantly correlated with antifungal activity, 5 had not previously been described from feijoa. Two novel cultivars were the most bioactive, and the compound 4-cyclopentene-1,3-dione, detected in these cultivars, was potently antifungal (IC₅₀ = 1–2 μM) against human-pathogenic <i>Candida</i> species. Haploinsufficiency and fluorescence microscopy analyses determined that the synthesis of chitin, a fungal-cell-wall polysaccharide, was the target of 4-cyclopentene-1,3-dione. This fungal-specific mechanism was consistent with a 22–70-fold reduction in antibacterial activity. Overall, we identified the agricultural waste product of specific cultivars of feijoa peels as a source of potential high-value antifungal compounds

Polyhalogenated Indoles from the Red Alga <i>Rhodophyllis membranacea</i>: The First Isolation of Bromo-Chloro-Iodo Secondary Metabolites

An unusual tetrahalogenated indole with the exceptionally rare inclusion of the three halogens bromine, chlorine, and iodine was found using mass spectrometry within a fraction of a semipurified extract obtained from the red alga <i>Rhodophyllis membranacea.</i> We report herein the isolation and structure elucidation, using a combination of NMR spectroscopy and mass spectrometry, of 11 new tetrahalogenated indoles (<b>1</b>–<b>11</b>), including four bromochloroiodoindoles (<b>5</b>–<b>7</b>, <b>10</b>). Several were evaluated for cytotoxic and antifungal activities against the HL-60 promyelocytic cell line and <i>Saccharomyces cerevisiae</i>, respectively