土壤通过滋养农作物、储存食物来源和容纳微生物来维持人类生命，这可能会影响次生代谢物的营养和生物合成，其中一些被用作药物。为了鉴定一类新药物的先导化合物，我们从包括城市地区在内的各种环境中收集了土壤来源的真菌菌株。由于各种人类病原体被认为会影响土壤真菌中代谢物的生物合成途径，从而导致新型支架的产生，因此我们将工作重点放在人口稠密的城市地区和旅游景点。针对 MDA-MB-231 细胞筛选土壤来源的真菌提取物文库，以获得其细胞毒性活性。值得注意的是，10μg/mL的贵州木霉提取物(DS9-1)被发现表现出71%的抑制效果。分级、分离和结构阐明工作导致鉴定出九种新的 peptaibols，trichoguizaibols A-I (1-9)，包含 14 个氨基酸残基 (14-AA peptaibols)，以及三种新的 peptaibols，trichoguizaibols J-L (10-12)，包含 18 个氨基酸残基（18-AA peptaibols）。 1-12 的化学结构是根据其一维和二维核磁共振谱、HRESIMS、电子圆二色性数据以及先进的 Marfey 方法的结果确定的。发现 18-AA peptaibols 对 MDA-MB-231、SK-Hep1、SKOV3、DU145 和 HCT116 细胞的细胞毒性大于 14-AA peptaibols。在这些化合物中，10-12 表现出有效的亚微摩尔 IC50 值。这些结果有望为开发新型支架作为抗癌药物指明新方向。

Soil sustains human life by nourishing crops, storing food sources, and housing microbes, which may affect the nutrition and biosynthesis of secondary metabolites, some of which are used as drugs. To identify lead compounds for a new class of drugs, we collected soil-derived fungal strains from various environments, including urban areas. As various human pathogens are assumed to influence the biosynthetic pathways of metabolites in soil fungi, leading to the production of novel scaffolds, we focused our work on densely populated urban areas and tourist attractions. A soil-derived fungal extract library was screened against MDA-MB-231 cells to derive their cytotoxic activity. Notably, 10 μg/mL of the extract of Trichoderma guizhouense (DS9-1) was found to exhibit an inhibitory effect of 71%. Fractionation, isolation, and structure elucidation efforts led to the identification of nine new peptaibols, trichoguizaibols A-I (1-9), comprising 14 amino acid residues (14-AA peptaibols), and three new peptaibols, trichoguizaibols J-L (10-12), comprising 18 amino acid residues (18-AA peptaibols). The chemical structures of 1-12 were determined based on their 1D and 2D NMR spectra, HRESIMS, electronic circular dichroism data, and results of the advanced Marfey's method. The 18-AA peptaibols were found to exhibit cytotoxicity against MDA-MB-231, SK-Hep1, SKOV3, DU145, and HCT116 cells greater than that of the 14-AA peptaibols. Among these compounds, 10-12 exhibited potent sub-micromolar IC50 values. These results are expected to shed light on a new direction for developing novel scaffolds as anticancer agents.