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首页> 外文期刊>Biophysical Chemistry: An International Journal Devoted to the Physical Chemistry of Biological Phenomena >Photophysical and thermodynamic evaluation on the in vitro and in silico binding profile of Camptothecin with DNA
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Photophysical and thermodynamic evaluation on the in vitro and in silico binding profile of Camptothecin with DNA

机译：在体外和DNA的硅胶粘附剖面上的光物理和热力学评价

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摘要

Camptothecin (CMT) is an anti-tumour alkaloid drug exhibiting selective topoisomerase-I inhibitory activity by eventually hindering dynamic functions of DNA duplex via initiating apoptosis. Unravelling the binding mechanism of CMT with bio macromolecular systems can offer fundamental information regarding the mechanism of actions which can lead to the design of rational proactive drugs. This study endeavoured the binding interactions of CMT with calf thymus DNA (ct-DNA) along with the structural alterations attained by the DNA duplex owing to CMT interactions through multi-spectroscopic, calorimetric and molecular docking studies. The UV-visible absorbance and fluorescence quenching studies revealed the binding strength of CMT with ct-DNA, evident from the binding constants K-1 = 3.79 x 10(3) M-1 and Kq = 2 x 10(3) M-1. The time-resolved lifetime measurements inferred that the quenching was static due to the non-fluorescent ground state complex formation. The dye displacement study, temperature melting and viscosity measurements established a typical non-intercalative binding mode of CMT with ct-DNA. The binding isotherm deduced from ITC was found to be spontaneous and exothermic exerting a promising Delta G value of -6.2 kcal mol(-1). The thermal kinetic parameters implied that the forces primarily involved in the CMT-ct-DNA complexation are hydrogen bonding and van der Waals interactions. Moreover, the structural alterations of DNA duplex reflected in the CD and FTIR spectra could undeniably confirm the groove binding manner of CMT. The in silica extra precision docking study explored more accurate molecular illustrations of sequence specific minor groove binding mechanism evolved between CMT and DNA corroborating well with the experimental results. These innovative findings may shorten the path towards the development of novel and more effective CMT drug derivatives.
机译：CamptiChin（CMT）是一种抗肿瘤生物碱药物，通过启动细胞凋亡最终通过最终阻碍DNA双链体的动态功能，表现出选择性拓扑异构酶-I抑制活性。解开CMT与生物宏分子系统的结合机制可以提供关于可能导致理性积极药物设计的动作机制的基本信息。该研究促进了CMT与小牛胸腺DNA（CT-DNA）的结合相互作用以及通过通过多光谱，热量和分子对接研究的CMT相互作用而获得的结构改变。 UV可见光吸光度和荧光猝灭研究显示CMT与CT-DNA的结合强度，从结合常数K-1 = 3.79×10（3）m-1和Kq = 2×10（3）m-1 。推断时分辨的寿命测量推断，由于非荧光接地状态复杂形成，淬火是静态的。染料位移研究，温度熔化和粘度测量建立了CT-DNA的CMT的典型非插入结合模式。发现从ITC推导的结合等温线被发现是自发性和放热的施加达到-6.2kcal摩尔（-1）的有希望的δG值。热动力学参数暗示主要涉及CMT-CT-DNA络合的力是氢键和范德华相互作用。此外，CD和FTIR光谱中反映的DNA双链体的结构改变可以无可否认地确认CMT的凹槽结合方式。在二氧化硅额外精度对接研究中探讨了更准确的分子说明的序列特异性小凹槽结合机构在CMT和DNA良好之间呈实验结果。这些创新的发现可能缩短了新颖和更有效的CMT药物衍生物的发展的路径。

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