Laboratory of Hybrid Materials, Chemistry Department, Federal University of São Paulo (UNIFESP), Diadema SP, Brazil.
Laboratory of Chemical Biology, Center for Natural and Human Sciences, Federal University of ABC (UFABC), Santo Andre SP, Brazil.
Bioorg Chem. 2022 Jul;124:105814. doi: 10.1016/j.bioorg.2022.105814. Epub 2022 Apr 18.
The present work evaluated the antiprotozoal activity of isolinderanolide E, isolated from the Brazilian plant Nectandra oppositifolia, against promastigote forms of Leishmania (Leishmania) amazonensis. The compound exhibited an EC value of 20.3 μM, similar to the positive control miltefosine (IC of 19.4 μM), and reduced toxicity to macrophages (CC > 200 μM). Based on these results, Langmuir monolayers of two unsaturated lipids: 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), were employed as a model of mammalian and parasite membranes, respectively, to study the interaction of isolinderanolide E at a molecular level. The films were characterized with tensiometry (surface pressure-area isotherms and surface pressure-time curves), infrared spectroscopy, and Brewster angle microscopy (BAM). This compound changed the profile of the isotherms leading to fluid DOPC and DOPE monolayers, which were not able to attain rigid states even with compression. Infrared spectroscopy showed that the bioactive compound decreases the trans/gauche ratio conformers related to the molecular conformational disorder. BAM showed the formation of specific aggregates upon drug incorporation. In conclusion, isolinderanolide E changes the thermodynamic, mechanical, structural, and morphological characteristics of the monolayer of these unsaturated lipids, which may be essential to understand the action at the molecular level bioactives in biointerfaces.
本研究评价了从巴西植物 Nectandra oppositifolia 中分离得到的异榄香脂醇 E 对前鞭毛体形式的利什曼原虫（Leishmania）亚马逊ensis 的抗原生动物活性。该化合物的 EC 值为 20.3 μM，与阳性对照米替福新（IC 为 19.4 μM）相似，对巨噬细胞的毒性较小（CC>200 μM）。基于这些结果，使用两种不饱和脂质的 Langmuir 单层：1,2-二油酰基-sn-甘油-3-磷酸胆碱（DOPC）和 1,2-二油酰基-sn-甘油-3-磷酸乙醇胺（DOPE），分别作为哺乳动物和寄生虫膜的模型，研究 isolinderanolide E 在分子水平上的相互作用。用张力仪（表面压力-面积等温线和表面压力-时间曲线）、红外光谱和布鲁斯特角显微镜（BAM）对薄膜进行了表征。该化合物改变了等温线的轮廓，导致 DOPC 和 DOPE 单层流体化，即使压缩也无法达到刚性状态。红外光谱表明，生物活性化合物降低了与分子构象无序相关的反式/ gauche 比构象体。BAM 显示药物掺入后形成了特定的聚集体。总之，异榄香脂醇 E 改变了这些不饱和脂质单层的热力学、力学、结构和形态特征，这对于理解生物界面中生物活性物质的分子水平作用可能是必不可少的。
