Shahabadi Nahid, Shiri Farshad, Hadidi Saba
a Inorganic Chemistry Department, Faculty of Chemistry , Razi University , Kermanshah , Iran.
b Medical Biology Research Center (MBRC) Kermanshah University of Medical Sciences , Kermanshah , Iran.
Nucleosides Nucleotides Nucleic Acids. 2018 Mar 4;37(3):147-168. doi: 10.1080/15257770.2018.1438617. Epub 2018 Feb 21.
The interaction between the dimer structure of ibuprofen drug (D-IB) and calf thymus DNA under simulative physiological conditions was investigated with the use of Hoechst 33258 and methylene blue dye as spectral probes by the methods of UV-visible absorption, fluorescence spectroscopy, circular dichroism spectroscopy and molecular modeling study.Using the Job's plot, a single class of binding sites for theD-IB on DNA was put in evidence. The Stern-Volmer analysis of fluorescence quenching data shows the presence of both the static and dynamic quenching mechanisms. The binding constants, K were calculated at different temperatures, and the thermodynamic parameters ∆G, ∆H and ∆S were given. The experimental results showed that D-IB molecules could bind with DNA via groove binding mode as evidenced by: I. DNA binding constant from spectrophotometric studies of the interaction of D-IB with DNA is comparable to groove binding drugs. II. Competitive fluorimetric studies with Hoechst 33258 have shown that D-IB exhibits the ability of this complex to displace with DNA-bounded Hoechst, indicating that it binds to DNA in strong competition with Hoechst for the groove binding. III. There is no significantly change in the absorption of the MB-DNA system upon adding the D-IB, indicates that MB molecules are not released from the DNA helix after addition of the D-IB and are indicative of a non-intercalative mode of binding. IV. Small changes in DNA viscosity in the presence of D-IB, indicating weak link to DNA, which is consistent with DNA groove binding. As well as, induced CD spectral changes, and the docking results revealed that groove mechanism is followed by D-IB to bind with DNA.
在模拟生理条件下，以Hoechst 33258和亚甲基蓝染料作为光谱探针，采用紫外可见吸收光谱、荧光光谱、圆二色光谱和分子模拟研究等方法，研究了布洛芬药物二聚体结构（D-IB）与小牛胸腺DNA之间的相互作用。通过Job曲线法，证明了D-IB在DNA上存在单一类型的结合位点。荧光猝灭数据的Stern-Volmer分析表明同时存在静态和动态猝灭机制。计算了不同温度下的结合常数K，并给出了热力学参数∆G、∆H和∆S。实验结果表明，D-IB分子可通过沟槽结合模式与DNA结合，具体依据如下：I. 通过D-IB与DNA相互作用的分光光度研究得到的DNA结合常数与沟槽结合药物相当。II. 与Hoechst 33258的竞争性荧光研究表明，D-IB具有使该复合物与DNA结合的Hoechst发生置换的能力，这表明它与Hoechst在与沟槽结合的竞争中与DNA强烈结合。III. 添加D-IB后，MB-DNA系统的吸收没有明显变化，这表明添加D-IB后MB分子没有从DNA螺旋中释放出来，表明其结合模式为非嵌入模式。IV. 在D-IB存在下DNA粘度的微小变化，表明与DNA的连接较弱，这与DNA沟槽结合一致。此外，诱导的圆二色光谱变化以及对接结果表明，D-IB遵循沟槽机制与DNA结合。
