Hierarchical Virtual Screening of Potential Insectides Inhibitors of Acetylcholinesterase and Juvenile Hormone from Temephos
by
Glauber V. da Costa 1,2,3,
Elenilze F. B. Ferreira 1,2,
Ryan da S. Ramos 2
,
Luciane B. da Silva 2,
Ester M. F. de Sá 3,
Alicia K. P. da Silva 3,
Cássio M. Lobato 3,
Raimundo N. P. Souto 4,
Carlos Henrique T. de P. da Silva 5,
Leonardo B. Federico 5,
Joaquín M. C. Rosa 6 and
Cleydson B. R. dos Santos 1,2,5,*
Glauber V. da Costa 1,2,3,
Elenilze F. B. Ferreira 1,2,
Ryan da S. Ramos 2,
Luciane B. da Silva 2,
Ester M. F. de Sá 3,
Alicia K. P. da Silva 3,
Cássio M. Lobato 3,
Raimundo N. P. Souto 4,
Carlos Henrique T. de P. da Silva 5,
Leonardo B. Federico 5,
Joaquín M. C. Rosa 6 and
Cleydson B. R. dos Santos 1,2,5,*
1
Postgraduate Program in-Network in Pharmaceutical Innovation, Federal University of Amapá, Macapá, AP 68902-280, Brazil
2
Laboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amapá, Macapá, AP 68902-280, Brazil
3
Laboratory of Biotechnology in Natural Products, Department of Biological and Health Sciences, Federal University of Amapá, Macapá, AP 68902-280, Brazil
4
Laboratory of Arthropoda, Federal University of Amapá, Macapá, AP 68902-280, Brazil
5
Computational Laboratory of Pharmaceutical Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, São Paulo 14040-903, Brazil
6
Department of Pharmaceutical and Organic Chemistry, Faculty of Pharmacy, Institute of Biosanitary Research ibs. GRANADA, University of Granada, 18071 Granada, Spain
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2019, 12(2), 61; https://doi.org/10.3390/ph12020061
Received: 25 February 2019 / Revised: 5 April 2019 / Accepted: 8 April 2019 / Published: 18 April 2019
(This article belongs to the Special Issue Design of Enzyme Inhibitors as Potential Drugs)
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.
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Keywords:
acetylcholinesterase; juvenile hormone; temephos; molecular docking
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MDPI and ACS Style
V. da Costa, G.; Ferreira, E.F.B.; da S. Ramos, R.; B. da Silva, L.; M. F. de Sá, E.; K. P. da Silva, A.; M. Lobato, C.; N. P. Souto, R.; T. de P. da Silva, C.H.; B. Federico, L.; M. C. Rosa, J.; B. R. dos Santos, C. Hierarchical Virtual Screening of Potential Insectides Inhibitors of Acetylcholinesterase and Juvenile Hormone from Temephos. Pharmaceuticals 2019, 12, 61.
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