Ayimbila Francis, Tantimongcolwat Tanawut, Ruankham Waralee, Pingaew Ratchanok, Prachayasittikul Veda, Prachayasittikul Virapong, Prachayasittikul Supaluk, Phopin Kamonrat
Center for Research Innovation and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok, 10700, Thailand.
Department of Clinical Chemistry, Faculty of Medical Technology, Mahidol University, Bangkok, 10700, Thailand.
Sci Rep. 2025 Jun 2;15(1):19249. doi: 10.1038/s41598-025-02787-1.
A set of 1,4-naphthoquinone (1,4-NQ) derivatives possesses various pharmaceutical activities. Among them, a synthetic 2-(4-methoxyanilino)naphthalene-1,4-dione (MN) is found to be non-cytotoxic to the normal MRC-5 cells and prevent neuronal SH-SY5Y cell damage. To explore the underlying interaction mechanism of MN in the circulatory system, in silico and multi-spectroscopic techniques were employed to investigate the complex of human serum albumin (HSA) and MN. The interaction between HSA and MN exhibited static fluorescence with a potential dynamic mechanism, as K×10 (M) decreased with increasing temperatures. Thermodynamic parameters and molecular dynamics (MD) simulations indicated a stable and spontaneous binding process driven by hydrophobic interactions and endothermic characteristics. Both circular dichroism (CD) and Fourier transform infrared (FT-IR) spectroscopy analyses revealed that MN induced conformational changes in HSA, affecting α-helix, β-turn, β-sheet, and random coil components, thereby altering the secondary structure of HSA. Competitive binding and molecular docking showed that MN preferentially binds to subdomain IIA in site I of HSA with the lowest binding affinity (‒7.15 kcal/mol), though it also has some affinities for subdomains IB and IIIA in site III and II, respectively. Additionally, the esterase activity of HSA showed no significant changes in the presence of MN. Understanding the binding interaction between MN and HSA provides valuable insights for further investigating the pharmacodynamic mechanism of MN and its potential applications in the area of medicinal chemistry.
一组1,4-萘醌（1,4-NQ）衍生物具有多种药理活性。其中，一种合成的2-（4-甲氧基苯胺基）萘-1,4-二酮（MN）被发现对正常的MRC-5细胞无细胞毒性，并能防止神经元SH-SY5Y细胞损伤。为了探究MN在循环系统中的潜在相互作用机制，采用计算机模拟和多光谱技术研究了人血清白蛋白（HSA）与MN的复合物。HSA与MN之间的相互作用表现出静态荧光且可能存在动态机制，因为随着温度升高，K×10（M）降低。热力学参数和分子动力学（MD）模拟表明，该结合过程稳定且自发，由疏水相互作用和吸热特性驱动。圆二色性（CD）和傅里叶变换红外（FT-IR）光谱分析均显示，MN诱导了HSA的构象变化，影响了α-螺旋、β-转角、β-折叠和无规卷曲成分，从而改变了HSA的二级结构。竞争性结合和分子对接表明，MN优先结合于HSA位点I的亚结构域IIA，结合亲和力最低（-7.15 kcal/mol），不过它对位点III的亚结构域IB和位点II的亚结构域IIIA也有一定亲和力。此外，在MN存在的情况下，HSA的酯酶活性没有显著变化。了解MN与HSA之间的结合相互作用，为进一步研究MN的药效学机制及其在药物化学领域的潜在应用提供了有价值的见解。
