土壤通过滋养作物来维持人类的生命,储存食物来源,和容纳微生物,这可能会影响次级代谢产物的营养和生物合成,其中一些被用作药物。为了确定一类新药的先导化合物,我们从各种环境中收集了土壤来源的真菌菌株,包括城市地区。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,导致新型脚手架的生产,我们的工作重点是人口稠密的城市地区和旅游景点。针对MDA-MB-231细胞筛选了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,发现10μg/mL的贵州木霉提取物(DS9-1)表现出71%的抑制作用。分馏,隔离,和结构阐明的努力导致了九个新的peptaibol的鉴定,trichoguizaibolsA-I(1-9),包含14个氨基酸残基(14-AA肽),和三个新的peptaibols,TrichoguizaibolsJ-L(10-12),包含18个氨基酸残基(18-AA肽)。1-12的化学结构是根据其1D和2DNMR光谱确定的,HRESIMS,电子圆二色性数据,以及先进的Marfey方法的结果。发现18-AA肽对MDA-MB-231,SK-Hep1,SKOV3,DU145和HCT116细胞的细胞毒性高于14-AA肽。在这些化合物中,图10-12显示出有效的亚微摩尔IC50值。这些结果有望为开发新型支架作为抗癌剂提供新的方向。
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.