Open AccessPromising Aedes aegypti Repellent Chemotypes Identified through Integrated QSAR, Virtual Screening, Synthesis, and Bioassay
Author(s) -
Polina V. Oliferenko,
Alexander A. Oliferenko,
Gennadiy Poda,
Dmitry I. Osolodkin,
Girinath G. Pillai,
Ulrich R. Bernier,
Maia Tsikolia,
Natasha M. Agramonte,
Gary G. Clark,
Kenneth J. Linthicum,
Alan R. Katritzky
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0064547
Subject(s) - aedes aegypti , bioassay , chikungunya , dengue fever , virtual screening , aedes , docking (animal) , biology , dengue virus , computational biology , drug discovery , virology , bioinformatics , veterinary medicine , medicine , ecology , larva
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.