Radiation & Photochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India.
Radiation & Photochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India.
Spectrochim Acta A Mol Biomol Spectrosc. 2018 Jun 15;199:394-402. doi: 10.1016/j.saa.2018.03.085. Epub 2018 Apr 3.
Curcumin isoxazole (CI) and Curcumin pyrazole (CP), the diketo modified derivatives of Curcumin (CU) are metabolically more stable and are being explored for pharmacological properties. One of the requirements in such activities is their interaction with circulatory proteins like human serum albumin (HSA). To understand this, the interactions of CI and CP with HSA have been investigated employing absorption and fluorescence spectroscopy and the results are compared with that of CU. The respective binding constants of CP, CI and CU with HSA were estimated to be 9.3×10, 8.4×10 and 2.5×10M, which decreased with increasing salt concentration in the medium. The extent of decrease in the binding constant was the highest in CP followed by CI and CU. This revealed that along with hydrophobic interaction other binding modes like electrostatic interactions operate between CP/CI/CU with HSA. Fluorescence quenching studies of HSA with these compounds suggested that both static and dynamic quenching mechanisms operate, where the contribution of static quenching is higher for CP and CI than that for CU. From fluorescence resonance energy transfer studies, the binding site of CU, CI and CP was found to be in domain IIA of HSA. CU was found to bind in closer proximity with Trp214 as compared to CI and CP and the same was responsible for efficient energy transfer and the same was also established by fluorescence anisotropy measurements. Furthermore docking simulation complemented the experimental observation, where both electrostatic as well as hydrophobic interactions were indicated between HSA and CP, CI and CU. This study is useful in designing more stable CU derivatives having suitable binding properties with proteins like HSA.
姜黄素异噁唑（CI）和姜黄素吡唑（CP）是姜黄素（CU）的二酮修饰衍生物，它们在代谢上更加稳定，并且正在探索其药理学特性。在这些研究中，其中一个要求是它们与循环蛋白（如人血清白蛋白（HSA））相互作用。为了理解这一点，已经使用吸收和荧光光谱法研究了 CI 和 CP 与 HSA 的相互作用，并将结果与 CU 的结果进行了比较。CP、CI 和 CU 与 HSA 的各自结合常数估计为 9.3×10、8.4×10 和 2.5×10M，这随着介质中盐浓度的增加而降低。结合常数的降低程度在 CP 最高，其次是 CI 和 CU。这表明，除了疏水相互作用外，CP/CI/CU 与 HSA 之间还存在其他结合模式，如静电相互作用。这些化合物对 HSA 的荧光猝灭研究表明，静态和动态猝灭机制都起作用，其中 CP 和 CI 的静态猝灭贡献高于 CU。从荧光共振能量转移研究中，发现 CU、CI 和 CP 的结合位点位于 HSA 的 IIA 结构域。与 CI 和 CP 相比，CU 被发现更靠近 Trp214 结合，这是有效能量转移的原因，这也通过荧光各向异性测量得到证实。此外，对接模拟补充了实验观察结果，表明 HSA 与 CP、CI 和 CU 之间存在静电和疏水相互作用。这项研究对于设计具有与 HSA 等蛋白质结合特性的更稳定的 CU 衍生物是有用的。
