LBM - Laboratory of Molecular Biology, Universidade Federal de Goiás, Goiânia, Goiás, 74690-900, Brazil.
Collaborative Nucleus of Biosystems, Universidade Federal de Goiás, Jataí, Goiás, 75804-020, Brazil.
Future Microbiol. 2019 Dec;14:1589-1606. doi: 10.2217/fmb-2019-0166. Epub 2020 Jan 28.
To perform virtual screening of compounds based on natural products targeting isocitrate lyase of . Homology modeling and molecular dynamics simulations were applied in order to obtain conformational models for virtual screening. The selected hits were tested against enzymatic activity of ICL of the dimorphic fungus and growth of the spp. The cytotoxicity and selectivity index of the compounds were defined. Carboxamide, lactone and β-carboline moieties were identified as interesting chemical groups for the design of new antifungal compounds. The compounds inhibited ICL of the dimorphic fungus activity. The compound 4559339 presented minimum inhibitory concentration of 7.3 μg/ml in with fungicidal effect at this concentration. Thus, a new potential antifungal against is proposed.
为了针对 异柠檬酸裂解酶对天然产物进行虚拟筛选，我们采用同源建模和分子动力学模拟的方法，获得了虚拟筛选的构象模型。我们对所选的化合物进行了酶活性抑制实验，实验对象为二相型真菌的 ICL 和 spp 的生长情况。我们定义了化合物的细胞毒性和选择性指数。我们发现，酰胺、内酯和β-咔啉部分是设计新型抗真菌化合物的有趣化学基团。所合成的化合物能够抑制二相型真菌的 ICL 活性。化合物 4559339 在 中的最低抑菌浓度为 7.3μg/ml，并且在该浓度下具有杀菌作用。因此，我们提出了一种针对 的新型潜在抗真菌药物。
