Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226001, India.
Eur J Med Chem. 2013 Apr;62:693-704. doi: 10.1016/j.ejmech.2013.01.017. Epub 2013 Jan 29.
Synthesis of novel 4-aminoquinoline-rhodanine hybrid using inexpensive starting materials via easy to operate methodology, and their biological activity is reported. All the compounds were screened for their in vitro antimalarial activity against chloroquine-resistant (K1) and chloroquine-sensitive (3D7) strains of Plasmodium falciparum, and their cytotoxicity toward VERO cell line. Compounds 9, 19, 21 and 23 exhibited excellent antimalarial activity with IC50 value ranging from 13.2 to 45.5 nM against chloroquine-resistant (K1) strain. Biochemical studies revealed that inhibition of hemozoin formation is the primary mechanism of action of these analogs for their antimalarial activity. Additionally, some derivatives (14, 18 and 26) of this series also exhibited the antimycobacterial activity against H37Rv strain of Mycobacterium tuberculosis with MIC value of 6.25 μM.
使用廉价起始原料通过易于操作的方法合成新型 4-氨基喹啉-缩二脲杂合化合物，并报告其生物活性。所有化合物均针对体外抗疟活性进行筛选，针对氯喹抗性（K1）和氯喹敏感（3D7）株疟原虫以及对 VERO 细胞系的细胞毒性。化合物 9、19、21 和 23 对氯喹抗性（K1）株表现出优异的抗疟活性，IC50 值范围为 13.2 至 45.5 nM。生化研究表明，抑制亚铁血红素形成是这些类似物抗疟活性的主要作用机制。此外，该系列的一些衍生物（14、18 和 26）对结核分枝杆菌 H37Rv 株也表现出抗分枝杆菌活性，MIC 值为 6.25 μM。
