Abstract：
Wedelolactone (WEL) is a small molecule compound isolated from Eclipta prostrate L., which has been reported to possess various biological activities such as anti-hepatotoxicity, anti-hypertension, anti-tumour, anti-phospholipase A2 and detoxification activity against snake venom. In the present study, we investigated the interaction of WEL with human serum albumin (HSA) using simultaneous fluorescence, UV-visible spectroscopy, 3D fluorescence spectroscopy, Fourier transform infrared spectroscopy (FTIR), molecular docking technique and molecular dynamics simulation. We found that the interaction between HSA and WEL can exhibit a static fluorescence burst mechanism, and the binding process is essentially spontaneous, with the main forces manifested as hydrogen bonding, van der Waals force and electrostatic interactions. Competitive binding and molecular docking studies showed that WEL preferentially bound to HSA in substructural region IIA (site I); molecular dynamics simulations showed that HSA interacted with WEL to form a stable complex, which also induced conformational changes in HSA. The study of the interaction between WEL and HSA can provide a reference for a more in-depth study of the pharmacodynamic mechanism of WEL and its further development and utilisation.
摘要：
Wedelolactone（WEL）是一种小分子化合物，分离自厄运。据报道，它具有多种生物活性，如抗肝毒性，抗高血压,抗肿瘤，抗磷脂酶A2和对蛇毒的解毒活性。在本研究中,我们使用同时荧光研究了WEL与人血清白蛋白（HSA）的相互作用，紫外可见光谱，三维荧光光谱,傅里叶变换红外光谱(FTIR),分子对接技术和分子动力学模拟。我们发现HSA和WEL之间的相互作用可以表现出静态荧光爆发机制，结合过程基本上是自发的，主要力量表现为氢键，范德华力和静电相互作用。竞争结合和分子对接研究表明,WEL优先与HSA结合的亚结构区IIA(位点I);分子动力学模拟表明,HSA与WEL相互作用形成稳定的复合物,这也诱导了HSA的构象变化。对WEL与HSA相互作用的研究可为更深入地研究WEL的药效学机制及其进一步开发利用提供参考。
