13种以前未描述的林得烷倍半萜二聚体(LSD),命名为氯酚醛G-S(1-13),从金钱草的整株植物中分离出来。什叶派,以及十种已知的类似物(14-23)。通过全面的光谱分析阐明了化合物1-13的结构和绝对构型,NMR和电子圆二色性(ECD)计算,和X射线单晶衍射。氯醇内酯G(1)代表通过C-15-C-9'碳-碳单键形成的LSD的第一个实例,还提出了其合理的生物合成途径。推断氯醇内酯I和J(3和4)是稀有的8,9-seco和9-脱氧LSD,具有C-11-C-7'碳-碳键,分别。评价了所有分离株对NLRP3炎性体激活的抑制活性,六个化合物(5、7、8、17、22和23)表现出显著的效果,和IC50值范围为2.99至8.73µM。此外,总结了有关其抑制NLRP3炎性体激活的初步结构-活性关系分析。在J774A.1细胞中,化合物17表现出对尼德霉素诱导的焦亡的剂量依赖性抑制。分子对接研究表明化合物17和NLRP3之间存在强相互作用。
Thirteen previously undescribed lindenane sesquiterpenoid dimers (LSDs), named chlorahololides G-S (1-13), were isolated from the whole plants of Chloranthus holostegius var. shimianensis, along with ten known analogues (14-23). The structures and absolute configurations of compounds 1-13 were elucidated through comprehensive spectroscopic analysis, NMR and electronic circular dichroism (ECD) calculations, and X-ray single-crystal diffraction. Chlorahololide G (1) represents the first instance of LSDs formed via a C-15-C-9\' carbon-carbon single bond, whose plausible biosynthetic pathway was also proposed. Chlorahololides I and J (3 and 4) were deduced to be rare 8,9-seco and 9-deoxy LSDs with C-11-C-7\' carbon-carbon bond, respectively. The inhibitory activity against NLRP3 inflammasome activation was evaluated for all isolates, with six compounds (5, 7, 8, 17, 22, and 23) exhibiting significant effects, and IC50 values ranging from 2.99 to 8.73 µM. Additionally, a preliminary structure-activity relationship analysis regarding their inhibition of NLRP3 inflammasome activation was summarized. Compound 17 exhibited dose-dependent inhibition of nigericin-induced pyroptosis in J774A.1 cells. Molecular docking studies suggested a strong interaction between compound 17 and NLRP3.