He Ling-Ling, Wang Zhi-Xin, Wang Yong-Xia, Liu Xian-Ping, Yang Yan-Jie, Gao Yan-Ping, Wang Xin, Liu Bin, Wang Xin
College of Applied Chemistry, Shenyang University of Chemical Technology, Shenyang 110142, China.
College of Pharmacy, Liaoning University, Shenyang 110036, China.
Colloids Surf B Biointerfaces. 2016 Sep 1;145:820-829. doi: 10.1016/j.colsurfb.2016.06.001. Epub 2016 Jun 2.
Fluorescence, absorption, time-correlated single photon counting (TCSPC), and circular dichroism (CD) spectroscopic techniques as well as molecular modeling methods were used to study the binding characterization of promethazine (PMT) to human serum albumin (HSA) and the influence of flavonoids, rutin and baicalin, on their affinity. The results indicated that the fluorescence quenching mechanism of HSA by PMT is a static quenching due to the formation of complex. The reaction was spontaneous and mainly mediated by hydrogen bonds and hydrophobic interactions. The binding distance between the tryptophan residue of HSA and PMT is less than 8nm, which indicated that the energy transfer from the tryptophan residue of HSA to PMT occurred. The binding site of PMT on HSA was located in sites I and the presence of PMT can cause the conformational changes of HSA. There was the competitive binding to HSA between PMT and flavonoids because of the overlap of binding sites in HSA. The flavonoids could decrease the association constant and increase the binding distance. In addition, their synergistic effect can further change the conformation of HSA. The decrease in the affinities of PMT binding to HSA in the presence of flavonoids may lead to the increase of free drug in blood, which would affect the transportation or disposition of drug and evoke an adverse or toxic effect. Hence, rationalising dosage and diet regimens should be taken into account in clinical application of PMT.
采用荧光、吸收、时间相关单光子计数（TCSPC）和圆二色性（CD）光谱技术以及分子模拟方法，研究了异丙嗪（PMT）与人血清白蛋白（HSA）的结合特性以及黄酮类化合物芦丁和黄芩苷对它们亲和力的影响。结果表明，PMT对HSA的荧光猝灭机制是由于复合物形成导致的静态猝灭。该反应是自发的，主要由氢键和疏水相互作用介导。HSA的色氨酸残基与PMT之间的结合距离小于8nm，这表明发生了从HSA的色氨酸残基到PMT的能量转移。PMT在HSA上的结合位点位于位点I，PMT的存在可导致HSA的构象变化。由于HSA中结合位点的重叠，PMT与黄酮类化合物之间存在对HSA的竞争性结合。黄酮类化合物可降低结合常数并增加结合距离。此外，它们的协同作用可进一步改变HSA的构象。在黄酮类化合物存在下，PMT与HSA结合亲和力的降低可能导致血液中游离药物的增加，这会影响药物的转运或处置并引发不良或毒性作用。因此，在PMT的临床应用中应考虑合理的剂量和饮食方案。
