Identification of novel <i>Aedes aegypti</i> odorant-binding protein 1 modulators by ligand and structure-based approaches and bioassays

Neto, Moysés Fagundes de Araújo; Santos, Cleydson Breno Rodrigues dos; Magalhães-Junior, Jairo Torres; Leite, Franco Henrique Andrade

doi:10.1080/07391102.2020.1808074

Cited by 8 publications

(9 citation statements)

References 58 publications

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“…Pharmacophore‐based approaches can help prioritize compounds with the same stereo‐electronic features of known active compounds and, thus, with the same mechanism [31–33] . Therefore, the pharmacophore model's flexible search of stereo‐electronic features is directly related to potent compounds, which can elucidate the compounds related to repellent activity in essential oils [13] …”

Section: Resultsmentioning

confidence: 99%

“…Ledol was the only compound of E. globulus essential oil that superimposed in pharmacophore (0.94 %; QFIT=41.95). Thus, the five compounds superimposed in the pharmacophore model have stereo‐electronic requirements for binding in Aaeg OBP1 and modulate the mosquito behavior [13] …”

Section: Resultsmentioning

confidence: 99%

“…A previously validated pharmacophore model for Ae. aegypti repellents [13] was employed in a flexible alignment with a dataset of 56, as available in the GALAHAD™ module [41] . Compounds were ranked according to QFIT values, and those with positive values were selected for molecular docking [41]…”

Section: Methodsmentioning

confidence: 99%

“…The conformational search and scoring evaluation were performed by Piecewise Linear Potential (ChemPLP) fitness function available on GOLD program 5.4.0 using the default parameters [13] . The compounds prioritized on pharmacophore‐based virtual screening were employed on a molecular docking routine, which employ the Genetic algorithm to flexibly consider ligands and active site in molecular docking study and, thus, find the most stable conformer of each compound [44] .…”

Section: Methodsmentioning

confidence: 99%

“…In vivo experiments (e. g., repellency tests) and computational strategies (e. g., pharmacophoric models and molecular coupling) integration with the use of natural agents is of great importance, whereas they aim to investigate these compounds’ effects against Ae. aegypti [12,13] . Additionally, both approaches are essential in the development of new repellents, since it involves estimating effective concentrations of a substance by measuring the biological response and hypothesizing a repellent mechanism in face of a specific target (e. g., Aaeg OBP1).…”

Section: Introductionmentioning

confidence: 99%

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Identification of Bioactive Compounds against Aedes aegypti (Diptera: Culicidae) by Bioassays and in Silico Assays

Brito

Oliveira

Silva

et al. 2021

Chemistry & Biodiversity

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Most of the hematophagous insects act as disease vectors, including Aedes aegypti, responsible for transmitting some of the most critical arboviruses globally, such as Dengue. The use of repellents based on natural products is a promising alternative for personal protection compared to industrial chemical repellents. In this study, the repellent effect of essential oils extracted from Lippia thymoides, Lippia alba, Cymbopogon winterianus, and Eucalyptus globulus leaves was evaluated. Essential oils used showed repellent activity against Ae. aegypti in laboratory bioassays, obtaining protection rates above 70 % from 3.75 mg/mL and higher concentration for all analyzed oils. GC/MS identified 57 constituents, which were used in the ligand‐based pharmacophore model to expose compounds with requirements for repellents that modulate mosquitoes behavior through odorant‐binding protein 1 Ae. aegypti. Ligand‐based pharmacophore model approach results suggested that repellent activity from C. winterianus, L. alba, and L. thymoides essential oils’ metabolites is related to Citronelal (QFIT=26.77), Citronelol (QFIT=11.29), Citronelol acetate (QFIT=52.22) and Geranil acetate (QFIT=10.28) with synergistic or individual activity. E. globulus essential oil's repellent activity is associated with Ledol (0.94 %; QFIT=41.95). Molecular docking was applied to understand the binding mode and affinity of the essential oils’ data set at the protein binding site. According to molecular docking, Citronelol (ChemPLP=60.98) and geranyl acetate (ChemPLP=60.55) were the best‐classified compounds compared to the others and they can be explored to develop new repellents.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Identification of Bioactive Compounds against Aedes aegypti (Diptera: Culicidae) by Bioassays and in Silico Assays

Brito

Oliveira

Silva

et al. 2021

Chemistry & Biodiversity

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A Combined Computational Methodology for the Discovery of Hit Compounds with Putative Insect Repellency Properties

et al. 2022

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Mosquitoes and other hematophagous arthropods, the primary vectors of multiple parasites and viruses, are responsible for the transmission of serious diseases to humans. Nowadays, the interest is focused on the development of novel repellents to the existing ones with advanced properties. The present study attempts the discovery of novel hit compounds which may evolve as insect repellents using a combined computational methodology targeting the Odorant Binding Protein 1 (OBP1). The in silico results indicated two compounds, namely coniferyl alcohol and 1,2‐diphenyl‐2‐propanol, which were further evaluated (a) in vitro for their binding affinity to AgamOBP1 and (b) in vivo using dose‐dependent repellence tests against the aggressive‐day biting Aedes albopictus. The combination of in vitro and in vivo results pointed that coniferyl alcohol and 1,2‐diphenyl‐2‐propanol exhibited high binding affinity over OBP1 with 69.4 and 84.7 nM, respectively as well as efficient repellent activity. Compounds were also tested for their dose‐dependent repellency activity in vivo against Aedes albopictus. Overall, the selected compounds can serve as scaffolds for the development of novel repellents.

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2D finger-printing and molecular docking studies identified potent mosquito repellents targeting odorant binding protein 1

Liggri

Pérez‐Garrido

Tsitsanou

et al. 2023

Insect Biochemistry and Molecular Biology

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Identification of novel Aedes aegypti odorant-binding protein 1 modulators by ligand and structure-based approaches and bioassays

Cited by 8 publications

References 58 publications

Identification of Bioactive Compounds against Aedes aegypti (Diptera: Culicidae) by Bioassays and in Silico Assays

Identification of Bioactive Compounds against Aedes aegypti (Diptera: Culicidae) by Bioassays and in Silico Assays

A Combined Computational Methodology for the Discovery of Hit Compounds with Putative Insect Repellency Properties

2D finger-printing and molecular docking studies identified potent mosquito repellents targeting odorant binding protein 1

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