Synthesis and insecticidal activity of novel pyrimidine derivatives containing urea pharmacophore against Aedes aegypti

Authors: LIU, XING-HAI - Zhejiang University; QIAO, WANG - Zhejiang University; SUN, ZHAO-HUI - Zhejiang University; Wedge, David; Becnel, James; ESTEP, ALDEN - Us Navy Medical Entomology Detachment; TAN, CHENG-XIA - Zhejiang University; WENG, JIAN-QUAN - Zhejiang University

Submitted to: Pest Management Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/19/2016
Publication Date: 4/1/2017
Citation: Liu, X., Qiao, W., Sun, Z., Wedge, D.E., Becnel, J.J., Estep, A.S., Tan, C., Weng, J. 2017. Synthesis and insecticidal activity of novel pyrimidine derivatives containing urea pharmacophore against Aedes aegypti. Pest Management Science. 73:953–959. doi:10.1002/ps.4370.

Interpretive Summary: Aedes aegypti is a major mosquito vector for the transmission of serious diseases, especially dengue and yellow fever. More than one billion people in developing countries are at risk. The widespread and continual use of pesticides can lead to resistant mosquitoes. In order to maintain mosquito control gains, it is critical to develop and evaluate novel bioactive molecules that differ in mode of action from currently used products. A series of synthetic molecules were synthesized and biological activity studied. Many of them exhibited insecticidal activity against adult and larval mosquitoes. This study suggests that these pyrimidine derivatives exhibited some activity against the yellow fever mosquito, and with further structure modification, could be novel lead compounds for the development of insecticides against mosquitoes.

Technical Abstract: Aedes aegypti is a major mosquito vector for the transmission of serious diseases, especially dengue and yellow fever. More than one billion people in developing countries are at risk. The widespread and continual use of pesticides can lead to resistant mosquitoes. In order to maintain mosquito control gains, it is critical to develop and evaluate novel bioactive molecules that differ in mode of action from currently used products. A series of novel pyrimidine derivatives were designed and synthesized. Their structures were elucidated by 1H NMR and HRMS. Biological activities of these compounds were tested against Aedes aegypti. Many of them exhibited insecticidal activity against adult and larval mosquitos. Compound 4d displayed relatively good activity to reach 70% mortality at 2 µg/mL. Furthermore, DFT (Density functional theory) calculations were established to study the structure-activity relationship of these novel compounds. A practical synthetic route for pyrimidine derivatives is presented. This study suggests that these pyrimidine derivatives exhibited some activity against the yellow fever mosquito, and, with further structure modification, could be novel lead compounds for the development of insecticides against mosquitos.