Abstract
Molecular field topology analysis, scaffold hopping, and molecular docking were used as complementary computational tools for the design of repellents for Aedes aegypti, the insect vector for yellow fever, chikungunya, and dengue fever. A large number of analogues were evaluated by virtual screening with Glide molecular docking software. This produced several dozen hits that were either synthesized or procured from commercial sources. Analysis of these compounds by a repellent bioassay resulted in a few highly active chemicals (in terms of minimum effective dosage) as viable candidates for further hit-to-lead and lead optimization effort.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adult
-
Aedes / drug effects*
-
Animals
-
Biological Assay
-
Cyclohexanols / chemistry*
-
Cyclohexanols / pharmacology
-
Female
-
Humans
-
Insect Repellents / chemistry*
-
Insect Repellents / pharmacology
-
Insect Vectors / drug effects*
-
Male
-
Molecular Docking Simulation
-
Quantitative Structure-Activity Relationship
Substances
-
Cyclohexanols
-
Insect Repellents
Grants and funding
This work was partly supported by the Deployed War-Fighter Protection Research Program and funded by the United States Department of Defense through the Armed Forces Pest Management Board. Funding for OICR is provided by the Ontario Ministry of Economic Development and Innovation, Ontario, Canada. No additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.