Knutsson_2017_Eur.J.Med.Chem_134_415

Reference

Title : N-Aryl-N'-ethyleneaminothioureas effectively inhibit acetylcholinesterase 1 from disease-transmitting mosquitoes - Knutsson_2017_Eur.J.Med.Chem_134_415
Author(s) : Knutsson S , Kindahl T , Engdahl C , Nikjoo D , Forsgren N , Kitur S , Ekstrom F , Kamau L , Linusson A
Ref : Eur Journal of Medicinal Chemistry , 134 :415 , 2017
Abstract :

Vector control of disease-transmitting mosquitoes by insecticides has a central role in reducing the number of parasitic- and viral infection cases. The currently used insecticides are efficient, but safety concerns and the development of insecticide-resistant mosquito strains warrant the search for alternative compound classes for vector control. Here, we have designed and synthesized thiourea-based compounds as non-covalent inhibitors of acetylcholinesterase 1 (AChE1) from the mosquitoes Anopheles gambiae (An. gambiae) and Aedes aegypti (Ae. aegypti), as well as a naturally occurring resistant-conferring mutant. The N-aryl-N'-ethyleneaminothioureas proved to be inhibitors of AChE1; the most efficient one showed submicromolar potency. Importantly, the inhibitors exhibited selectivity over the human AChE (hAChE), which is desirable for new insecticides. The structure-activity relationship (SAR) analysis of the thioureas revealed that small changes in the chemical structure had a large effect on inhibition capacity. The thioureas showed to have different SAR when inhibiting AChE1 and hAChE, respectively, enabling an investigation of structure-selectivity relationships. Furthermore, insecticidal activity was demonstrated using adult and larvae An. gambiae and Ae. aegypti mosquitoes.

PubMedSearch : Knutsson_2017_Eur.J.Med.Chem_134_415
PubMedID: 28433681
Gene_locus related to this paper: anoga-ACHE1

Related information

Inhibitor AL237
Gene_locus AL237    anoga-ACHE1

Citations formats

Knutsson S, Kindahl T, Engdahl C, Nikjoo D, Forsgren N, Kitur S, Ekstrom F, Kamau L, Linusson A (2017)
N-Aryl-N'-ethyleneaminothioureas effectively inhibit acetylcholinesterase 1 from disease-transmitting mosquitoes
Eur Journal of Medicinal Chemistry 134 :415

Knutsson S, Kindahl T, Engdahl C, Nikjoo D, Forsgren N, Kitur S, Ekstrom F, Kamau L, Linusson A (2017)
Eur Journal of Medicinal Chemistry 134 :415