| Summary: | <i>Penicillium setosum</i> represents a <i>Penicillium</i> species recently described, with little up-to-date information about its metabolic and biological potential. Due to this scenario, we performed chemical and biological studies of <i>P. setosum</i> CMLD18, a strain isolated from <i>Swinglea glutinosa</i> (Rutaceae). HRMS-MS guided dereplication strategies and anti-leukemia assays conducted the isolation and characterization of six compounds after several chromatographic procedures: 2-chloroemodic acid (<b>2</b>), 2-chloro-1,3,8-trihydroxy-6- (hydroxymethyl)-anthraquinone (<b>7</b>), 7-chloroemodin (<b>8</b>), bisdethiobis(methylthio)acetylaranotine (<b>9</b>), fellutanine C (<b>10</b>), and 4-methyl-5,6-diihydro-2H-pyran-2-one (<b>15</b>). From the assayed metabolites, (<b>10</b>) induced cellular death against Kasumi-1, a human leukemia cell line, as well as good selectivity for it, displaying promising cytotoxic activity. Here, the correct NMR signal assignments for (<b>9</b>) are also described. Therefore, this work highlights more detailed knowledge about the <i>P. setosum</i> chemical profile as well as its biological potential, offering prospects for obtaining natural products with anti-leukemia capabilities.
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