Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Department of Chemistry, Faculty of Science and Technology, Al-Neelain University, Khartoum, Sudan.
PLoS One. 2017 Apr 18;12(4):e0176015. doi: 10.1371/journal.pone.0176015. eCollection 2017.
Linifanib (LNF) possess antitumor activity and acts by inhibiting receptor tyrosine kinase VEGF and PDGF. The interaction of BSA with the drug can provide valuable information regarding the pharmacokinetic and pharmacodynamics behavior of drug. In our study the spectrophotometric methods and molecular docking studies were executed to understand the interaction behavior of BSA and LNF. BSA has an intrinsic fluorescence and that fluorescence was quenched by LNF. This quenching process was studied at three different temperatures of 288, 300and 308 K. The interaction between LNF and BSA was due to static quenching because the Ksv (Stern-Volmer constant) at 288 K was higher than at 300 and 308 K. Kq (quenching rate constant) behaved in a similar fashion as the Ksv. Several other parameters like binding constants, number of binding sites and binding energy in addition to molecular docking studies were also used to evaluate the interaction process. A decrease in the binding constants was observed with increasing temperatures and the binding site number approximated unity. The decreasing binding constant indicates LNF-BSA complex stability. The site mark competition experiment confirmed the binding site for LNF was located on site II of BSA. UV-visible studies along with synchronous fluorescence confirm a small change in the conformation of BSA upon interaction with LNF. The thermodynamic analysis provided the values for free energy ΔG0, ΔH0 and ΔS0. The ΔG0 at the 288, 300 and 308 K ranged in between -21.5 to -23.3 kJ mol-1, whereas the calculated values of ΔH (-55.91 kJ mol-1) and ΔS0 (-111.74 J mol-1·K-1). The experimental and molecular docking results suggest that the interaction between LNF and BSA was spontaneous and they exhibited hydrogen bonding and van der Waals force between them.
利尼伐尼（LNF）具有抗肿瘤活性，通过抑制受体酪氨酸激酶 VEGF 和 PDGF 发挥作用。BSA 与药物的相互作用可以提供有关药物药代动力学和药效学行为的有价值信息。在我们的研究中，执行了分光光度法和分子对接研究，以了解 BSA 和 LNF 的相互作用行为。BSA 具有固有荧光，并且该荧光被 LNF 猝灭。在 288、300 和 308 K 的三个不同温度下研究了猝灭过程。LNF 和 BSA 之间的相互作用是由于静态猝灭引起的，因为 288 K 时的 Ksv（斯特恩-沃尔默常数）高于 300 和 308 K。Kq（猝灭速率常数）的行为与 Ksv 相似。还使用了其他几个参数，如结合常数、结合位点数量和结合能，以及分子对接研究，以评估相互作用过程。随着温度的升高，观察到结合常数的降低，并且结合位点数量接近 1。结合常数的降低表明 LNF-BSA 配合物的稳定性。位点标记竞争实验证实 LNF 的结合位点位于 BSA 的 II 位。紫外-可见研究以及同步荧光证实了 BSA 与 LNF 相互作用后构象的微小变化。热力学分析提供了自由能ΔG0、ΔH0 和ΔS0 的值。在 288、300 和 308 K 下，ΔG0 的范围在-21.5 至-23.3 kJ mol-1 之间，而计算出的ΔH（-55.91 kJ mol-1）和ΔS0（-111.74 J mol-1·K-1）的值。实验和分子对接结果表明，LNF 与 BSA 之间的相互作用是自发的，它们之间存在氢键和范德华力。
