Shahabadi Nahid, Bagheri Somayeh
Department of Chemistry, Faculty of Science, Razi University, Kermanshah, Iran.
Department of Chemistry, Faculty of Science, Razi University, Kermanshah, Iran.
Spectrochim Acta A Mol Biomol Spectrosc. 2015 Feb 5;136 Pt C:1454-9. doi: 10.1016/j.saa.2014.10.036. Epub 2014 Oct 31.
The present study investigated the binding interaction between olanzapine and calf thymus DNA (ct-DNA) using emission, absorption, circular dichroism, viscosity measurements and molecular modeling. Thermodynamic parameters (ΔH<0 and ΔS<0) indicated that hydrogen bond and van der Waals play main roles in the binding of the drug to ct-DNA. Spectrophotometric studies of the interaction of olanzapine with DNA have shown that it could bind to ct-DNA (Kb=2×10(3)M(-1)). The binding constant is comparable to standard groove binding drugs. Competitive fluorimetric studies with Hoechst 33258 have shown that olanzapine exhibits the ability to displace the DNA-bound Hoechst 33258 indicating that binds strongly in minor groove of DNA helix. Furthermore, the drug induces detectable changes in the CD spectrum of ct-DNA as well as changes in its viscosity. All of the experimental results prove that the groove binding must be predominant. The results obtained from experimental data were in good agreement with molecular modeling studies.
本研究采用发射光谱、吸收光谱、圆二色光谱、粘度测量和分子模拟等方法，研究了奥氮平与小牛胸腺DNA（ct-DNA）之间的结合相互作用。热力学参数（ΔH<0和ΔS<0）表明，氢键和范德华力在药物与ct-DNA的结合中起主要作用。对奥氮平与DNA相互作用的分光光度研究表明，它可以与ct-DNA结合（Kb=2×10(3)M(-1)）。该结合常数与标准沟结合药物相当。与Hoechst 33258的竞争性荧光研究表明，奥氮平具有取代与DNA结合的Hoechst 33258的能力，这表明它在DNA螺旋的小沟中结合紧密。此外，该药物会引起ct-DNA的CD光谱以及其粘度的可检测变化。所有实验结果都证明沟结合一定是主要的。从实验数据获得的结果与分子模拟研究结果吻合良好。
