Naumowicz Monika, Zając Marcin, Kusaczuk Magdalena, Gál Miroslav, Kotyńska Joanna
Department of Physical Chemistry, Faculty of Chemistry, University of Bialystok, K. Ciolkowskiego 1K, 15-245 Bialystok, Poland.
Doctoral School of Exact and Natural Sciences, University of Bialystok, K. Ciolkowskiego 1K, 15-245 Bialystok, Poland.
Membranes (Basel). 2020 Nov 15;10(11):343. doi: 10.3390/membranes10110343.
Pharmacological efficiency of active compounds is largely determined by their membrane permeability. Thus, identification of drug-membrane interactions seems to be a crucial element determining drug-like properties of chemical agents. Yet, knowledge of this issue is still lacking. Since chemoprevention based on natural compounds such as cinnamic acid (CinA), -coumaric acid (-CoA) and ferulic (FA) is becoming a strong trend in modern oncopharmacology, determination of physicochemical properties of these anticancer compounds is highly important. Here, electrophoretic light scattering and impedance spectroscopy were applied to study the effects of these phenolic acids on electrical properties of bilayers formed from 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-diacyl-sn-glycero-3-phospho-l-serine (PS) or DOPC-PS mixture. After phenolic acid treatment, the negative charge of membranes increased in alkaline pH solutions, but not in acidic ones. The impedance data showed elevated values of both the electrical capacitance and the electrical resistance. We concluded that at acidic pH all tested compounds were able to solubilize into the membrane and permeate it. At neutral and alkaline pH, the CinA could be partially inserted into the bilayers, whereas -CoA and FA could be anchored at the bilayer surface. Our results indicate that the electrochemical methods might be crucial for predicting pharmacological activity and bioavailability of phenolic acids.
活性化合物的药理效率很大程度上取决于它们的膜通透性。因此，确定药物与膜的相互作用似乎是决定化学药剂类药物性质的关键因素。然而，目前仍缺乏关于这个问题的知识。由于基于肉桂酸（CinA）、香豆酸（-CoA）和阿魏酸（FA）等天然化合物的化学预防在现代肿瘤药理学中已成为一种强劲趋势，因此确定这些抗癌化合物的物理化学性质非常重要。在此，应用电泳光散射和阻抗谱来研究这些酚酸对由1,2-二油酰基-sn-甘油-3-磷酸胆碱（DOPC）、1,2-二酰基-sn-甘油-3-磷酸-L-丝氨酸（PS）或DOPC-PS混合物形成的双层膜电学性质的影响。酚酸处理后，膜的负电荷在碱性pH溶液中增加，但在酸性溶液中没有增加。阻抗数据显示电容和电阻值均升高。我们得出结论，在酸性pH下，所有测试化合物都能够溶解到膜中并渗透过膜。在中性和碱性pH下，CinA可以部分插入双层膜中，而-CoA和FA可以锚定在双层膜表面。我们的结果表明，电化学方法对于预测酚酸的药理活性和生物利用度可能至关重要。
