PDF(Pubmed)
Abstract：
Talaromyces, a filamentous fungus widely distributed across terrestrial and marine environments, can produce a diverse array of natural products, including alkaloids, polyketones, and polyketide-terpenoids. Among these, chrodrimanins represented a typical class of natural products. In this study, we isolated three previously undescribed pentaketide-sesquiterpenes, 8,9-epi-chrodrimanins (1-3), along with eight known compounds (4-11). The structures of compounds 1-3 were elucidated using nuclear magnetic resonance (NMR) and mass spectrometry (MS), while their absolute configurations were determined through X-ray crystallography and electronic circular dichroism (ECD) computations. The biosynthetic pathways of compounds 1-3 initiate with 6-hydroxymellein and involve multiple stages of isoprenylation, cyclization, oxidation, and acetylation. We selected four strains of gastrointestinal cancer cells for activity evaluation. We found that compound 3 selectively inhibited MKN-45, whereas compounds 1 and 2 exhibited no significant inhibitory activity against the four cell lines. These findings suggested that 8,9-epi-chrodrimanins could serve as scaffold compounds for further structural modifications, potentially leading to the development of targeted therapies for gastric cancer.
摘要：
Talaromyces,一种广泛分布在陆地和海洋环境中的丝状真菌，可以生产各种各样的天然产品，包括生物碱,聚酮,和聚酮-萜类化合物。其中,chrodrimanins代表了一类典型的天然产物。在这项研究中,我们分离出三个以前没有描述过的五酮倍半萜，8,9-epi-chrodrimanins(1-3),连同8种已知化合物(4-11)。使用核磁共振(NMR)和质谱(MS)阐明化合物1-3的结构,而它们的绝对构型是通过X射线晶体学和电子圆二色性（ECD）计算确定的。化合物1-3的生物合成途径以6-羟基mellein开始，并涉及多个阶段的异戊二烯化，环化,氧化，和乙酰化。我们选择了四株胃肠道癌细胞进行活性评估。我们发现化合物3选择性地抑制MKN-45,而化合物1和2对四种细胞系没有表现出显著的抑制活性。这些发现表明，8,9-表-铬甘露苷可以作为支架化合物进行进一步的结构修饰，可能导致胃癌靶向治疗的发展。
