Dipartimento di Farmacia, Università di Pisa, Via Bonanno 33, 56126 Pisa, Italy; Centro Interdipartimentale di Ricerca "Nutraceutica e Alimentazione per la Salute", Università di Pisa, via del Borghetto 80, 56124 Pisa, Italy.
Dipartimento di Farmacia, Università di Pisa, Via Bonanno 33, 56126 Pisa, Italy.
Fitoterapia. 2018 Oct;130:251-258. doi: 10.1016/j.fitote.2018.09.010. Epub 2018 Sep 18.
As a part of our ongoing research program on compounds from higher plants with lactate dehydrogenase (LDH) and monoacylglycerol lipase (MAGL) inhibitory activities, three new neoclerodane diterpene 12-deacetylsplendidin C (1), pseudorosmaricin (2), and 2-dehydroxysalvileucanthsin A (3) along with six known compounds were isolated from Salvia pseudorosmarinus aerial part extracts. Their structures were determined by spectroscopic and spectrometric techniques including 1D- and 2D NMR, and MS analyses. The isolated diterpenes were assayed for their inhibitory activity on LDH5 and MAGL, two enzymes covering key roles in the peculiar energetic metabolism of malignant tumours. All the assayed diterpenes showed negligible activity on LDH5, whereas the known jewenol A (4) displayed a moderate inhibition activity on MAGL, showing an IC value of 46.8μM and it proved to be a reversible MAGL inhibitor. Docking and molecular dynamic simulation studies where thus performed to evaluate the binding mode of 4 within MAGL.
作为我们正在进行的具有乳酸脱氢酶 (LDH) 和单酰基甘油脂肪酶 (MAGL) 抑制活性的高等植物化合物研究计划的一部分，从 Salvia pseudorosmarinus 地上部分提取物中分离得到了三个新的新克氏二萜 12-去乙酰splendidin C（1）、伪迷迭香酸（2）和 2-去羟化salvileucanthsin A（3）以及六个已知化合物。通过光谱和光谱技术，包括 1D 和 2D NMR 和 MS 分析，确定了它们的结构。对分离得到的二萜进行了对 LDH5 和 MAGL 的抑制活性测定，这两种酶在恶性肿瘤特有的能量代谢中起着关键作用。所有测定的二萜对 LDH5 的活性都可以忽略不计，而已知的 jewenol A（4）对 MAGL 显示出中等抑制活性，IC 值为 46.8μM，并且被证明是 MAGL 的可逆抑制剂。因此进行了对接和分子动力学模拟研究，以评估 4 在 MAGL 中的结合模式。
