OSMAC strategy is a useful tool for discovering series of metabolites from microorganism. Five new sambutoxin derivatives (–, , –), together with seven known compounds (, –, –), were isolated from sp. CY-3 under OSMAC strategy and guidance of molecular networking. Their planar structures and absolute configurations were determined by NMR, HRESIMS, ECD spectra and common biosynthetic pathway. In bioassay, compounds – showed cytotoxicity to tumor cell lines with IC values in the range of 1.76–49.13 μM. The antitumor molecular mechanism of was also explored. compound significantly inhibited the growth and proliferation of two lung cancer cell lines (A549 and H1703). Furthermore, colony formation, EdU analysis, flow cytometry and Western blot analysis showed that could induce cell cycle arrest in G0/G1 phase by promoting the expression of p53 and p21. The molecular mechanism of its antitumor effects is that arrests the cell cycle by activating the p21/CyclinD1/Rb signaling pathway and the p53 pathway. Our results identified a lead small molecule compound with efficient antitumor growth and proliferation activity.

中文翻译：

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红树林内生真菌 Talaromyces sp. 产生的具有抗肿瘤活性的 4-Hydroxy-2-pyridone 衍生物。 CY-3


OSMAC策略是从微生物中发现一系列代谢物的有用工具。从 sp. 中分离出五种新的三布毒素衍生物 (–, , –) 以及七种已知化合物 (, –, –)。 OSMAC策略和分子网络指导下的CY-3。通过NMR、HRESIMS、ECD谱和常见的生物合成途径确定了它们的平面结构和绝对构型。在生物测定中，化合物对肿瘤细胞系表现出细胞毒性，IC 值在 1.76–49.13 μM 范围内。还探讨了其抗肿瘤分子机制。化合物显着抑制两种肺癌细胞系（A549 和 H1703）的生长和增殖。此外，集落形成、EdU分析、流式细胞术和Western blot分析表明，它可以通过促进p53和p21的表达来诱导细胞周期停滞在G0/G1期。其抗肿瘤作用的分子机制是通过激活p21/CyclinD1/Rb信号通路和p53通路来阻滞细胞周期。我们的结果确定了一种具有有效抗肿瘤生长和增殖活性的先导小分子化合物。