Aragón-Muriel Alberto, Liscano Yamil, Morales-Morales David, Polo-Cerón Dorian, Oñate-Garzón Jose
Laboratorio de Investigación en Catálisis y Procesos (LICAP), Departamento de Química, Facultad de Ciencias Naturales y Exactas, Universidad del Valle, Cali 760031, Colombia.
Grupo de Investigación en Química y Biotecnología (QUIBIO), Facultad de Ciencias Básicas, Universidad Santiago de Cali, Cali 760035, Colombia.
Membranes (Basel). 2021 Jun 16;11(6):449. doi: 10.3390/membranes11060449.
Biological membranes are complex dynamic systems composed of a great variety of carbohydrates, lipids, and proteins, which together play a pivotal role in the protection of organisms and through which the interchange of different substances is regulated in the cell. Given the complexity of membranes, models mimicking them provide a convenient way to study and better understand their mechanisms of action and their interactions with biologically active compounds. Thus, in the present study, a new Schiff base () derivative from 2-(-aminophenyl)benzimidazole and 2,4-dihydroxybenzaldehyde was synthesized and characterized by spectroscopic and spectrometric techniques. Interaction studies of () with two synthetic membrane models prepared with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and DMPC/1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG) 3:1 mixture, imitating eukaryotic and prokaryotic membranes, respectively, were performed by applying differential scanning calorimetry (DSC). Molecular dynamics simulations were also developed to better understand their interactions. In vitro and in silico assays provided approaches to understand the effect of on these lipid systems. The DSC results showed that, at low compound concentrations, the effects were similar in both membrane models. By increasing the concentration of , the DMPC/DMPG membrane exhibited greater fluidity as a result of the interaction with . On the other hand, molecular dynamics studies carried out on the erythrocyte membrane model using the phospholipids POPE (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine), SM (N-(15Z-tetracosenoyl)-sphing-4-enine-1-phosphocholine), and POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) revealed that after 30 ns of interaction, both hydrophobic interactions and hydrogen bonds were responsible for the affinity of for PE and SM. The interactions of the imine with POPG (1-Palmitoyl-2-Oleoyl-sn-Glycero-3-Phosphoglycerol) in the membrane model were mainly based on hydrophobic interactions.
生物膜是由多种碳水化合物、脂质和蛋白质组成的复杂动态系统，它们共同在保护生物体方面发挥关键作用，并且细胞内不同物质的交换通过生物膜进行调节。鉴于膜的复杂性，模仿它们的模型为研究和更好地理解其作用机制以及它们与生物活性化合物的相互作用提供了一种便捷的方式。因此，在本研究中，合成了一种由2-（-氨基苯基）苯并咪唑和2,4-二羟基苯甲醛衍生的新型席夫碱（），并通过光谱和光谱技术对其进行了表征。通过差示扫描量热法（DSC）对（）与分别用1,2-二肉豆蔻酰-sn-甘油-3-磷酸胆碱（DMPC）和DMPC/1,2-二肉豆蔻酰-sn-甘油-3-磷酸甘油（DMPG）3:1混合物制备的两种合成膜模型的相互作用进行了研究，这两种模型分别模拟真核生物膜和原核生物膜。还开展了分子动力学模拟以更好地理解它们的相互作用。体外和计算机模拟分析提供了理解对这些脂质系统影响的方法。DSC结果表明，在低化合物浓度下，两种膜模型中的效应相似。随着浓度的增加，由于与的相互作用，DMPC/DMPG膜表现出更大的流动性。另一方面，使用磷脂POPE（1-棕榈酰-2-油酰-sn-甘油-3-磷酸乙醇胺）、SM（N-（15Z-二十四碳烯酰基）-鞘氨醇-4-烯-1-磷酸胆碱）和POPC（1-棕榈酰-2-油酰-sn-甘油-3-磷酸胆碱）在红细胞膜模型上进行的分子动力学研究表明，在30纳秒的相互作用后，疏水相互作用和氢键都导致了对PE和SM的亲和力。在膜模型中，亚胺与POPG（1-棕榈酰-2-油酰-sn-甘油-3-磷酸甘油）的相互作用主要基于疏水相互作用。
