新型4-氨基喹啉-1,3,5-三嗪衍生物对野生型和突变型疟原虫的合成、对接、体外及体内抗疟活性研究
Synthesis, Docking, In Vitro and In Vivo Antimalarial Activity of Hybrid 4-aminoquinoline-1,3,5-triazine Derivatives Against Wild and Mutant Malaria Parasites.
作者信息
Bhat Hans Raj, Singh Udaya Pratap, Gahtori Prashant, Ghosh Surajit Kumar, Gogoi Kabita, Prakash Anil, Singh Ramendra K
机构信息
Drug Design and Discovery Laboratory, Department of Pharmaceutical Sciences, Sam Higginbottom Institute of Agriculture Technology and Science, Deemed University, Allahabad, 211007, India.
Nucleic Acids and Antiviral Research Laboratory, Department of Chemistry, University of Allahabad, Allahabad, 211002, India.
出版信息
Chem Biol Drug Des. 2015 Sep;86(3):265-71. doi: 10.1111/cbdd.12490. Epub 2015 Jan 16.
A new series of hybrid 4-aminoquinoline-1,3,5-triazine derivatives was synthesized by a four-step reaction. Target compounds were screened for in vitro antimalarial activity against chloroquine-sensitive (3D-7) and chloroquine-resistant (RKL-2) strains of Plasmodium falciparum. Compounds exhibited, by and large, good antimalarial activity against the resistant strain, while two of them, that is 8g and 8a, displayed higher activity against both the strains of P. falciparum. Additionally, docking study was performed on both wild (1J3I.pdb) and quadruple mutant (N51I, C59R, S108 N, I164L, 3QG2.pdb) type pf-DHFR-TS to highlight the structural features of hybrid molecules.
通过四步反应合成了一系列新型的4-氨基喹啉-1,3,5-三嗪杂化衍生物。对目标化合物进行了针对恶性疟原虫氯喹敏感株（3D-7）和氯喹耐药株（RKL-2）的体外抗疟活性筛选。总体而言，这些化合物对耐药株表现出良好的抗疟活性，其中8g和8a这两种化合物对恶性疟原虫的两种菌株均表现出更高的活性。此外，还对野生型（1J3I.pdb）和四重突变型（N51I、C59R、S108N、I164L，3QG2.pdb）的pf-DHFR-TS进行了对接研究，以突出杂化分子的结构特征。
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