Laboratory of Biophysics, Intercollegiate Faculty of Biotechnology UG-MUG, Kładki 24, 80-822, Gdańsk, Poland.
Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308, Gdańsk, Poland.
Chem Biol Interact. 2015 Dec 5;242:291-8. doi: 10.1016/j.cbi.2015.10.008. Epub 2015 Oct 21.
Pentoxifylline--biologically active aromatic compound--has a well established capability to sequester aromatic ligands, such as an anticancer drug--doxorubicin--in mixed stacking aggregates. Formation of such hetero-complexes may influence biological activity of secluded drug. Presented work shows assessment of pentoxifylline influence on doxorubicin direct interactions with DNA employing biophysical methods. Achievement of this goal required statistical-thermodynamical model allowing numerical four-parameter analysis of experimental mixture--an issue that was successfully tackled by merging McGhee--von Hippel and Kapuscinski--Kimmel models. Results obtained with new model are well in agreement with data obtained with separate experiments with each of these two models and show reduction of doxorubicin in free (monomeric, dimeric) and complexed with DNA forms in favor of doxorubicin-pentoxifylline complexes with increasing pentoxifylline concentration. Developed model appears to be a universal tool allowing numerical analysis of mixtures containing self-aggregating ligand, DNA, and modulating agent.
己酮可可碱——一种具有生物活性的芳香族化合物——具有很好的螯合芳香族配体的能力，如抗癌药物——阿霉素——在混合堆积聚集体中。这种异质配合物的形成可能会影响被隔离药物的生物活性。目前的工作表明，采用生物物理方法评估己酮可可碱对阿霉素与 DNA 直接相互作用的影响。实现这一目标需要一个统计热力学模型，该模型允许对实验混合物进行四参数数值分析，这一问题通过合并 McGhee-von Hippel 和 Kapuscinski-Kimmel 模型成功解决。新模型得到的结果与使用这两个模型中的每一个进行单独实验得到的数据非常吻合，表明随着己酮可可碱浓度的增加，阿霉素在游离（单体、二聚体）和与 DNA 结合的形式中减少，有利于阿霉素-己酮可可碱复合物的形成。开发的模型似乎是一个通用工具，允许对含有自聚集配体、DNA 和调节剂的混合物进行数值分析。
