Hierarchical Virtual Screening of Potential Insectides Inhibitors of Acetylcholinesterase and Juvenile Hormone from Temephos
Metadata
Show full item recordEditorial
MDPI
Materia
Acetylcholinesterase Juvenile hormone Temephos Molecular docking
Date
2019-04-18Referencia bibliográfica
V da Costa, G., Ferreira, E. F., da S Ramos, R., B da Silva, L., MF de Sá, E., KP da Silva, A., ... & B Federico, L. (2019). Hierarchical Virtual Screening of Potential Insectides Inhibitors of Acetylcholinesterase and Juvenile Hormone from Temephos. Pharmaceuticals, 12(2), 61.
Abstract
Aedes aegypti (Linnaeus, 1762; Diptera: Culicidae) is the main vector transmitting viral
diseases such as dengue fever, dengue haemorrhagic fever, urban yellow fever, zika and chikungunya.
Worldwide, especially in the Americas and Brazil, many cases of dengue have been reported in
recent years, which have shown significant growth. The main control strategy is the elimination
of the vector, carried out through various education programs, to change human habits, but the
most usual is biological control, together with environmental management and chemical control.
The most commonly insecticide used is temephos (an organophosphorus compound), but Aedes
aegypti populations have shown resistance and the product is highly toxic, so we chose it as a template
molecule to perform a ligand-based virtual screening in the ChemBrigde (DIVERSet-CL subcollection)
database, searching for derivatives with similarity in shape (ROCS) and electrostatic potential (EON).
Thus, fourty-five molecules were filtered based on their pharmacokinetic and toxicological properties
and 11 molecules were selected by a molecular docking study, including binding affinity and mode
of interaction. The L46, L66 and L68 molecules show potential inhibitory activity for both the
insect (-9.28, -10.08 and -6.78 kcal/mol, respectively) and human (-6.05, 6.25 and 7.2 kcal/mol
respectively) enzymes, as well as the juvenile hormone protein (-9.2; -10.96 and -8.16 kcal/mol,
respectively), showing a significant difference in comparison to the template molecule temephos.
Molecules L46, L66 and L68 interacted with important amino acids at each catalytic site of the enzyme
reported in the literature. Thus, the molecules here investigated are potential inhibitors for both the
acetylcholinesterase enzymes and juvenile hormone protein–from insect and humans, characterizing
them as a potential insecticide against the Aedes aegypti mosquito.