Department of Technology, Universidade Estadual de Maringá, Av. Ângelo Moreira da Fonseca, 1800, 87506-370 Umuarama, PR, Brazil.
Department of Clinical Analysis & Biomedicine, Universidade Estadual de Maringá, Av. Colombo 5790, 87020-900 Maringá, PR, Brazil.
Future Microbiol. 2019 Jul;14:969-980. doi: 10.2217/fmb-2019-0052. Epub 2019 Aug 6.
A structural model of chorismate synthase (CS) from the pathogenic fungus was used for virtual screening simulations. Docking, molecular dynamics, cell growth inhibition and protein binding assays were used for search and validation. Two molecules termed CS8 and CaCS02 were identified. Further studies of the minimal inhibitory concentration demonstrated fungicidal activity against with a minimal inhibitory concentration and minimal fungicidal concentration of 512 and 32 μg·ml for CS8 and CaCS02, respectively. In addition, CaCS02 showed a strong synergistic effect in combination with amphotericin B without cytotoxic effects. studies using recombinant CS from showed IC of 29 μM for CaCS02 supporting our interpretation that inhibition of CS causes the observed fungicidal activity.
采用致病真菌分支杆菌（）色氨酸合酶（CS）的结构模型进行虚拟筛选模拟。采用对接、分子动力学、细胞生长抑制和蛋白质结合测定法进行搜索和验证。鉴定出两种称为 CS8 和 CaCS02 的分子。进一步研究最小抑菌浓度表明 CS8 和 CaCS02 对 具有杀菌活性，最小抑菌浓度和最小杀菌浓度分别为 512 和 32 μg·ml。此外，CaCS02 与两性霉素 B 联合使用具有很强的协同作用，且无细胞毒性作用。使用来自 的重组 CS 进行的研究显示 CaCS02 的 IC 为 29 μM，支持我们的解释，即 CS 的抑制导致观察到的杀菌活性。
