Bergmann Timna C, Menssen Max, Schotte Carsten, Cox Russell J, Lee-Thedieck Cornelia
Institute of Cell Biology and Biophysics, Department of Cell Biology, Leibniz University Hannover, 30419, Hannover, Germany.
Institute of Cell Biology and Biophysics, Department of Biostatistics, Leibniz University Hannover, 30419, Hannover, Germany.
Heliyon. 2024 Sep 13;10(22):e37713. doi: 10.1016/j.heliyon.2024.e37713. eCollection 2024 Nov 30.
Fungal specialized metabolites are known for their potent biological activities, among which tropolone sesquiterpenoids (TS) stand out for their diverse bioactivities. Here, we report cytotoxic and proliferation inhibitory effects of the recently discovered TS compounds 4-hydroxyxenovulene B and 4-dihydroxy norpycnidione, and the structurally related 4-hydroxy norxenovulene B and xenovulene B. Inhibition of metabolic activity after TS treatment was observed in Jurkat, PC-3 and FAIK3-5 cells, whereas MDA-MB-231 cells were unresponsive to treatment. Structurally similar epolones were shown to induce erythropoietin (EPO). Therefore, FAIK3-5 cells, which can naturally produce EPO, were applied to test the compounds in this regard. While no effect on EPO production in FAIK3-5 cells could be demonstrated, effects on their proliferation, viability, and morphology were observed depending on the presence of tropolone moieties in the molecules. Our study underlines the importance of relevant cell models for bioactivity testing of compounds with unknown mechanisms of action.
真菌特殊代谢产物以其强大的生物活性而闻名，其中托酚酮倍半萜（TS）因其多样的生物活性而格外突出。在此，我们报告了最近发现的TS化合物4-羟基新戊烯B和4-二羟基降吡啶二酮，以及结构相关的4-羟基去甲新戊烯B和新戊烯B的细胞毒性和增殖抑制作用。在Jurkat、PC-3和FAIK3-5细胞中观察到TS处理后代谢活性受到抑制，而MDA-MB-231细胞对处理无反应。结构相似的埃坡霉素被证明可诱导促红细胞生成素（EPO）。因此，能够天然产生EPO的FAIK3-5细胞被用于测试这些化合物在这方面的作用。虽然未证明对FAIK3-5细胞中EPO的产生有影响，但根据分子中托酚酮部分的存在情况，观察到了对其增殖、活力和形态的影响。我们的研究强调了相关细胞模型对于作用机制未知的化合物进行生物活性测试的重要性。
