Gupta Amit K, Varshney Kanika, Kumar Vivek, Srivastava Kumkum, Pant Aditya B, Puri Sunil K, Saxena Anil K
Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow, India.
In Vitro Toxicology Laboratory, CSIR-Indian Institute of Toxicology Research, Lucknow, India.
Arch Pharm (Weinheim). 2017 Apr;350(3-4). doi: 10.1002/ardp.201600335. Epub 2017 Feb 16.
A series of substituted 1,2,4-trioxanes were synthesized and evaluated for their antimalarial potential, in silico ADME properties and cytotoxicity on neuronal cell lines. Among the 15 synthesized substituted 1,2,4-trioxanes, two compounds (compound 15, IC = 25.71 nM; compound 21, IC = 19.6 nM) exhibited promising in vitro antimalarial potential comparable to those of the existing drugs chloroquine and artemisinin. Both of these compounds were found to be nontoxic up to 20 µM concentration in neuronal PC-12 cells. Compound 21 may serve as an optimized lead compound because of its less in vitro toxicity and lower probability to cross the blood brain barrier.
合成了一系列取代的1,2,4 -三恶烷，并对其抗疟潜力、计算机辅助药物代谢动力学（ADME）性质以及对神经元细胞系的细胞毒性进行了评估。在合成的15种取代的1,2,4 -三恶烷中，两种化合物（化合物15，IC = 25.71 nM；化合物21，IC = 19.6 nM）表现出与现有药物氯喹和青蒿素相当的有前景的体外抗疟潜力。在神经元PC - 12细胞中，发现这两种化合物在浓度高达20 μM时均无毒。由于化合物21的体外毒性较小且穿过血脑屏障的可能性较低，它可能作为一种优化的先导化合物。
