Department of Chemistry-IChTM, University of Belgrade, Njegoševa 12, 11000 Belgrade, Serbia.
Innovation Center of the Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, 11000 Belgrade, Serbia.
Spectrochim Acta A Mol Biomol Spectrosc. 2018 Mar 5;192:128-139. doi: 10.1016/j.saa.2017.10.061. Epub 2017 Nov 9.
Interactions between eight in-house synthesized aminoquinolines, along with well-known chloroquine, and human serum albumin (HSA) have been studied by fluorescence spectroscopy. The synthesized aminoquinolines, despite being structurally diverse, were found to be very potent antimalarials. Fluorescence measurements indicate that three compounds having additional thiophene or benzothiophene substructure bind more strongly to HSA than other studied compounds. Competitive binding experiments indicate that these three compounds bind significantly stronger to warfarin compared to diazepam binding site. Fluorescence quenching at three temperatures (20, 25, and 37°C) was analyzed using classical Stern-Volmer equation, and a static quenching mechanism was proposed. The enthalpy and entropy changes upon sulphur-containing compound-HSA interactions were calculated using Van't Hoff equation. Positive values of enthalpy and entropy changes indicate that non-specific, hydrophobic interactions are the main contributors to HSA-compound interaction. Molecular docking and calculated lipophilicity descriptors indicate the same, pointing out that the increased lipophilicity of sulphur-containing compounds might be a reason for their better binding to HSA. Obtained results might contribute to design of novel derivatives with improved pharmacokinetic properties and drug efficacy.
八种内合成的氨基喹啉与已知的氯喹与人血清白蛋白（HSA）的相互作用已通过荧光光谱法进行了研究。尽管合成的氨基喹啉结构多样，但它们被发现是非常有效的抗疟药物。荧光测量表明，具有额外噻吩或苯并噻吩结构的三种化合物与 HSA 的结合比其他研究化合物更强。竞争结合实验表明，与地西泮结合位点相比，这三种化合物与华法林的结合强度显著增强。在三个温度（20、25 和 37°C）下使用经典的 Stern-Volmer 方程分析了荧光猝灭，并提出了静态猝灭机制。使用 Van't Hoff 方程计算了含硫化合物-HSA 相互作用的焓变和熵变。焓变和熵变的正值表明，非特异性、疏水相互作用是 HSA-化合物相互作用的主要贡献者。分子对接和计算的亲脂性描述符表明情况相同，指出含硫化合物的亲脂性增加可能是它们与 HSA 更好结合的原因。获得的结果可能有助于设计具有改善的药代动力学性质和药物功效的新型衍生物。
