Green and Medicinal Chemistry Lab, Department of Chemistry, Osmania University, Hyderabad, Telangana State, 500 007, India.
Molecular Modeling and Medicinal Chemistry group, Department of Chemistry, Osmania University, Hyderabad, Telangana State, 500 007, India.
Mol Divers. 2017 Nov;21(4):999-1010. doi: 10.1007/s11030-017-9779-y. Epub 2017 Aug 24.
On the basis of reported antimycobacterial property of chroman-4-one pharmacophore, a series of chemically modified bis-spirochromanones were synthesized starting from 2-hydroxyacetophenone and 1,4-dioxaspiro[4.5] decan-8-one using a Kabbe condensation approach. The synthesized bis-spirochromanones were established based on their spectral data and X-ray crystal structure of 6e. All synthesized compounds were evaluated against Mycobacterium tuberculosis H37Rv (ATCC 27294) strain, finding that some products exhibited good antimycobacterial activity with minimum inhibitory concentration as low as [Formula: see text]. Docking studies were carried out to identify the binding interactions of compounds II, 6a and 6n with FtsZ. Compounds exhibiting good in vitro potency in the MTB MIC assay were further evaluated for toxicity using the HEK cell line.
基于色满-4-酮药效团的报道的抗分枝杆菌性质，我们从 2-羟基苯乙酮和 1,4-二氧杂螺[4.5]癸烷-8-酮开始，使用 Kabbe 缩合方法合成了一系列化学修饰的双螺[色满-4,3'-吡咯烷]。基于其光谱数据和 6e 的 X 射线晶体结构确定了合成的双螺[色满-4,3'-吡咯烷]。所有合成的化合物均针对结核分枝杆菌 H37Rv（ATCC 27294）菌株进行了评估，发现一些产物表现出良好的抗分枝杆菌活性，最低抑菌浓度低至[公式：见正文]。进行了对接研究以确定化合物 II、6a 和 6n 与 FtsZ 的结合相互作用。在 MTB MIC 测定中表现出良好的体外效力的化合物进一步使用 HEK 细胞系评估了毒性。
