两种卷叶草科植物干花蕾的乙醇提取物,金银花和阿贝丽娅×大花,对三磷酸腺苷(ATP)-柠檬酸裂解酶(ACL)表现出相当大的抑制活性,用于治疗代谢紊乱的新的有希望的药物靶标。生物测定指导的纯化与HPLC-PDA分析相结合,从上述两种植物提取物中分离出35种(1-35)和14种(1'-14')结构不同的化合物,分别。化合物1-9和1'-6'是先前未描述的糖苷。根据光谱数据阐明了它们的结构,电子圆二色性(ECD),和单晶X射线衍射分析。特别是,lonicejaposideA(1)具有前所未有的骨架,该骨架是通过羟醛缩合作用使secologanin中的C-7与苯乙醛中的C-2''偶联而产生的。AbelifflorosidesA(1')和B(2')是迄今为止未知的通过形成1,3-二恶烷部分而构建的三萜和双烷都结合物的糖苷。评价所有分离株对ACL的抑制活性。化合物9,25-28,31,1',2\',和14显示出显著的抑制作用,IC50值范围为0.1至14.2μM。具有不同结构特征的所选化合物的相互作用(例如,随后通过采用分子对接研究进行了9、25、31和2')与ACL的研究。此外,化合物2\',本文报道的最复杂的三萜-双西列酮偶联糖苷,还抑制乙酰辅酶A羧化酶1(ACC1),IC50值为7.9μM。日本金银花花蕾的干燥材料(金银花)是一种众所周知的传统东方药物(即,金银花,FLJ),并已长期大量使用。上述发现不仅为医疗保健社区中多功能利用FLJ的发展提供了新的见解,而且还提供了有利可图的线索,表明A.×grandiflora的花蕾可能是中药市场上FLJ的潜在替代品。
The ethanolic extracts of the dried flower buds of two Caprifoliaceae plants, Lonicera japonica and Abelia × grandiflora, showed considerable inhibitory activities against adenosine triphosphate (ATP)-citrate lyase (ACL), a new promising drug target for the treatment of metabolic disorders. Bioassay-guided purification in conjunction with HPLC-PDA profiling led to the isolation and characterization of thirty-five (1-35) and fourteen (1\'-14\') structurally diverse compounds from the above two plant extracts, respectively. Compounds 1-9 and 1\'-6\' are previously undescribed glycosides. Their structures were elucidated on the basis of spectroscopic data, electronic circular dichroism (ECD), and single crystal X-ray diffraction analyses. In particular, lonicejaposide A (1) has an unprecedented skeleton generated through the coupling of C-7 in secologanin with C-2\'\' in phenylacetaldehyde via an aldol condensation. Abeliflorosides A (1\') and B (2\') are hitherto unknown glycosides of triterpene and bisiridoid conjugates constructed through the formation of a 1,3-dioxane moiety. All the isolates were evaluated for their inhibitory activities against ACL. Compounds 9, 25-28, 31, 1\', 2\', and 14\' displayed significant inhibitory effects, with IC50 values ranging from 0.1 to 14.2 μM. The interactions of selected compounds possessing different structure features (e.g., 9, 25, 31, and 2\') with ACL were thereafter performed by employing molecular docking studies. In addition, compound 2\', the most complex triterpene-bisiridoid conjugate glycoside reported herein, also inhibited acetyl-CoA carboxylase 1 (ACC1), with an IC50 value of 7.9 μM. The dried material of the flower buds of L. japonica (honeysuckle) is a well-known traditional oriental medicine (i.e., Flos Lonicerae Japonicae, FLJ) and has long been used in large quantities. The above findings not only provide new insights for the development of multipurpose utilization of FLJ in healthcare community, but also provide profitable clues indicating that the flower buds of A. × grandiflora might be a potential alternative to FLJ in the traditional Chinese medicine market.