Laboratory of Hybrid Materials, Chemistry Department, Federal University of São Paulo, Diadema, SP, Brazil.
Laboratory of Chemical Biology, Center for Natural and Human Sciences, Federal University of ABC, Brazil.
Biochim Biophys Acta Biomembr. 2021 Feb 1;1863(2):183500. doi: 10.1016/j.bbamem.2020.183500. Epub 2020 Oct 29.
The polymerization of bioactive compounds may be interesting because the supramolecular structures formed can boost biological action on microorganism membranes. In the present work, poly-thymolformaldehyde (PTF) activity, prepared by condensation of thymol and formaldehyde, was evaluated against trypomastigote forms of Trypanosoma cruzi and related with the physicochemical changes provided by the incorporation of the compound in protozoan cell membrane models. PTF exhibited an EC value of 23.4 μg/mL and no toxicity against mammalian cells (CC > 200 μg/mL). To understand the molecular action of PTF as an antiprotozoal candidate, this compound was incorporated in Langmuir monolayers of dipalmitoylphosphatidylglycerol (DPPG) as a model for parasite cell membranes. PTF shifted DPPG surface pressure-area isotherms to higher areas, indicating its incorporation in the lipid films. Additionally, it changed the thermodynamic, compressional, structural, and morphological properties of the floating monolayers, decreasing the collapse pressure, reducing the surface elasticity, and segregating molecules at the interface, forming domains with different reflectivities. Infrared spectroscopy showed that the lipid films with PTF presented an increased rate of gauche/all-trans conformers for the methylene groups from the acyl chains, indicating molecular disorder. Therefore, these results show that PTF alters the physicochemical properties of DPPG monolayers as a model for protozoa cell membranes, which can enhance the comprehension of the parasitic action of PTF against T. cruzi.
生物活性化合物的聚合可能很有趣，因为形成的超分子结构可以增强对微生物膜的生物作用。在本工作中，通过缩合百里酚和甲醛制备的聚百里酚甲醛（PTF）对锥虫Trypanosoma cruzi的动质体形式的活性进行了评估，并与该化合物在原生动物细胞膜模型中引起的理化变化相关联。PTF 表现出 23.4μg/mL 的 EC 值，并且对哺乳动物细胞没有毒性（CC>200μg/mL）。为了了解 PTF 作为抗原生动物候选物的分子作用，将该化合物掺入二棕榈酰磷脂酰甘油（DPPG）的 Langmuir 单层中，作为寄生虫细胞膜的模型。PTF 将 DPPG 的表面压力-面积等温线推向更高的区域，表明其掺入脂质膜中。此外，它改变了浮动单层的热力学、压缩、结构和形态特性，降低了坍塌压力，降低了表面弹性，并使分子在界面处分离，形成具有不同反射率的域。红外光谱表明，含有 PTF 的脂质膜中，来自酰基链的亚甲基的顺式/反式构象比率增加，表明分子无序。因此，这些结果表明，PTF 改变了 DPPG 单层作为原生动物细胞膜模型的物理化学性质，这可以增强对 PTF 对 T. cruzi 的寄生作用的理解。
