856437-30-4Relevant academic research and scientific papers
Discovery of Selective Inhibitors Targeting Acetylcholinesterase 1 from Disease-Transmitting Mosquitoes
Engdahl, Cecilia,Knutsson, Sofie,Ekstr?m, Fredrik,Linusson, Anna
, p. 9409 - 9421 (2016/11/11)
Vector control of disease-transmitting mosquitoes is increasingly important due to the re-emergence and spread of infections such as malaria and dengue. We have conducted a high throughput screen (HTS) of 17,500 compounds for inhibition of the essential AChE1 enzymes from the mosquitoes Anopheles gambiae and Aedes aegypti. In a differential HTS analysis including the human AChE, several structurally diverse, potent, and selective noncovalent AChE1 inhibitors were discovered. For example, a phenoxyacetamide-based inhibitor was identified with a 100-fold selectivity for the mosquito over the human enzyme. The compound also inhibited a resistance conferring mutant of AChE1. Structure-selectivity relationships could be proposed based on the enzymes' 3D structures; the hits' selectivity profiles appear to be linked to differences in two loops that affect the structure of the entire active site. Noncovalent inhibitors of AChE1, such as the ones presented here, provide valuable starting points toward insecticides and are complementary to existing and new covalent inhibitors.
Searching for the Multi-Target-Directed Ligands against Alzheimer's disease: Discovery of quinoxaline-based hybrid compounds with AChE, H 3R and BACE 1 inhibitory activities
Huang, Wenhai,Tang, Li,Shi, Ying,Huang, Shufang,Xu, Lei,Sheng, Rong,Wu, Peng,Li, Jia,Zhou, Naiming,Hu, Yongzhou
experimental part, p. 7158 - 7167 (2012/02/05)
A novel series of quinoxaline derivatives, as Multi-Target-Directed Ligands (MTDLs) for AD treatment, were designed by lending the core structural elements required for H3R antagonists and hybridizing BACE 1 inhibitor 1 with AChE inhibitor BYYT
