【摘要】 为了研究一种来自真菌茎点霉Phoma-L29的次级代谢产物（R）-（-）-蜂蜜曲菌素的抗氧化性能及药用潜力，该文采用分光光度法从清除O₂^-·自由基、DPPH·自由基及抑制Fe²⁺诱导卵黄脂蛋白脂质的过氧化作用3方面考察了该化合物的抗氧化活性，并辅以高斯理论计算解释。采用荧光光谱法和分子对接技术考察了该化合物与作为药物载体蛋白的人血清白蛋白（HSA）的结合以及对HSA蛋白质构象的影响。结果表明，（R）-（-）-蜂蜜曲菌素能有效清除O₂^-·自由基和DPPH·自由基，可抑制Fe²⁺诱导卵黄脂蛋白脂质的过氧化作用，尤其对O₂^-·自由基表现出较强的清除能力，其IC₅₀值低至1.92μmol·L^-1。（R）-（-）-蜂蜜曲菌素的前线分子轨道能量计算结果合理解释了该化合物的抗氧化活性。（R）-（-）-蜂蜜曲菌素与HSA结合形成了1∶1的复合物，在298 K和310 K下的结合常数K_a分别为1.064×10⁴、6.51×10³ L·mol^-1。这种结合对HSA的蛋白质构象基本不产生影响，二者之间作用力主要为氢键和范德华力，且二者之间的结合距离（3.54 nm）表明（R）-（-）-蜂蜜曲菌素与HSA之间能够发生非辐射能量转移。分子对接结果显示，（R）-（-）-蜂蜜曲菌素位于HSA分子ⅢA亚域（位点Ⅱ）的疏水空腔，二者之间形成了4个广泛氢键，分别对应于氨基酸残基Arg-485、Leu-481、Arg-348和Arg-348。（R）-（-）-蜂蜜曲菌素的抗氧化活性及其对蛋白质构象影响的研究结果可为评估（R）-（-）-蜂蜜曲菌素的药用前景提供实验基础和理论依据。更多还原

【Abstract】 (R)-（-）-Mellein as a secondary metabolite from endophytic fungi Phoma-L29 was studied to understand its antioxidant properties and medicinal potential in this article.The antioxidation activity of（R）-（-）-mellein was detected for clearance of O₂^-·radical and DPPH·radical and inhibition of Fe²⁺-induced lipid peroxidation in yolk lipoprotein by spectrophotometry,which was supplemented by Gaussian theory calculation explanation.In order to examine the combination of （R）-（-）-mellein with human serum albumin（HSA） as a drug carrier protein and the influence on the conformation of HSA protein,the interaction between （R）-（-）-mellein and HSA was investigated by fluorescence spectrometry and molecular docking technology.The results showed that （R）-（-）-mellein cleared O₂^-·and DPPH·radicals and inhibited lipid peroxidation effectively and it especially exhibited stronger clearance ability for O₂^-·radical with an IC₅₀ value of 1.92μmol·L^-1.The calculated frontier molecular orbital energy supplied a reasonable explanation for its antioxidation activity.（R）-（-）-mellein combined with HSA to form a 1∶1 complex and the binding constants were 1.064×10⁴ L·mol^-1 and 6.51×10³ L·mol^-1.Little impact on HSA protein conformation was observed during their combination and the hydrogen bond and van der Waals force were the main forces for （R）-（-）-mellein-HSA complex.The binding distance with 3.54 nm meant that non-radiative energy transfer occurred between （R）-（-）-mellein and HSA.Molecular docking result explored that（R）-（-）-mellein molecule was located in the hydrophobic cavity of protein subdomain ⅢA（siteⅡ）and there were four broad hydrogen bonds in the complex molecule which corresponded to amino acid residues Arg-485,Leu-481,Arg-348 and Arg-348.These results of antioxidation activity and effect on HSA protein conformation could provide the experiment and the theory basis for the evaluation of the medicinal prospects of （R）-（-）-mellein.更多还原