Promising Aedes aegypti Repellent Chemotypes Identified through Integrated QSAR, Virtual Screening, Synthesis, and Bioassay

Oliferenko, Polina V.; Oliferenko, Alexander A.; Poda, Gennadiy; Osolodkin, Dmitry I.; Pillai, Girinath G.; Bernier, Ulrich R.; Tsikolia, Maia; Agramonte, Natasha M.; Clark, Gary G.; Linthicum, Kenneth J.; Katritzky, Alan R.

doi:10.1371/journal.pone.0064547

Cited by 46 publications

(67 citation statements)

References 65 publications

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“…To circumvent this hurdle, a computational approach has been tested and proven to be effective (Boyle et al 2016a; Katritzky et al 2008, 2010; Oliferenko et al 2013). These approaches generally rely on identifying physicochemical descriptors that can be predictive of repellent behavioral activity from previously identified compounds like DEET and picaridin, among others.…”

Section: Activation Of Olfactory Receptors Dedicated To Aversionmentioning

confidence: 99%

Olfactory Mechanisms for Discovery of Odorants to Reduce Insect-Host Contact

Clark

Ray

2016

J Chem Ecol

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Insects have developed highly sophisticated and sensitive olfactory systems to find animal or plant hosts for feeding. Some insects vector pathogens that cause diseases in hundreds of millions of people and destroy billions of dollars of food products every year. There is great interest, therefore, in understanding how the insect olfactory system can be manipulated to reduce their contact with hosts. Here, we review recent advances in our understanding of insect olfactory detection mechanisms, which may serve as a foundation for designing insect control programs based on manipulation of their behaviors by using odorants. Because every insect species has a unique set of olfactory receptors and olfactory-mediated behaviors, we focus primarily on general principles of odor detection that potentially apply to most insects. While these mechanisms have emerged from studies on model systems for study of insect olfaction, such as Drosophila melanogaster, they provide a foundation for discovery of odorants to repel insects or reduce host-seeking behavior.

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Section: Activation Of Olfactory Receptors Dedicated To Aversionmentioning

confidence: 99%

Olfactory Mechanisms for Discovery of Odorants to Reduce Insect-Host Contact

Clark

Ray

2016

J Chem Ecol

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“…constituted the basis of most of the 2D, 3D modelling applications subsequently developed . This data set was sometimes enlarged with compounds synthesized after selection of the most promising structures from screening important databases with a neural net classifier …”

Section: Introductionmentioning

confidence: 99%

“…On another hand, beside the role of molecular electronic characteristics, the influence of the actual geometry of molecules was taken into account in some 3D approaches. These approaches relied on the concept of pharmacophore, encoded for diastereoisomerism, or characterized docking with specific receptors . Oliferenko et al .…”

Section: Introductionmentioning

confidence: 99%

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Topological QSAR Modelling of Carboxamides Repellent Activity to Aedes Aegypti

Doucet

Doucet-Panaye

Papa

2019

Molecular Informatics

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Aedes aegypti vector control is of paramount importance owing to the damages induced by the various severe diseases that these insects may transmit, and the increasing risk of important outbreaks of these pathologies. Search for new chemicals efficient against Aedes aegypti, and devoid of side-effects, which have been associated to the currently most used active substance i. e. N,N-diethyl-mtoluamide (DEET), is therefore an important issue. In this context, we developed various Quantitative Structure Activity Relationship (QSAR) models to predict the repellent activity against Aedes aegypti of 43 carboxamides, by using Multiple Linear Regression (MLR) and various machine learning approaches. The easy computation of the four topological descriptors selected in this study, compared to the CODESSA descriptors used in the literature, and the predictive ability of the here proposed MLR and machine learning models developed using the software QSARINS and R, make the here proposed QSARs attractive. As demonstrated in this study, these models can be applied at the screening level, to guide the design of new alternatives to DEET.

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“…A chemical informatics approach was developed to address these challenges in which 34 carboximides and 34 N-acylpiperidines were predicted from quantitative-structure-activity models (CODESSA PRO) using USDA archived repellency data for DEET derivatives. These compounds were synthesized and behaviorally tested to show greater biological efficacy than DEET [52–54]. In a related approach, a specific set of physiochemical DRAGON descriptors was identified from the repellents in these studies and used to train a Support Vector Machine [43].…”

Section: Introductionmentioning

confidence: 99%

Reception of odors and repellents in mosquitoes

Ray

2015

Current Opinion in Neurobiology

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Mosquitoes use their sense of smell to find hosts, nectar, and oviposition sites, and to avoid repellents. A small number of mosquito species are adapted to feed on humans and have a major impact on public health by transmitting malaria, dengue, filariasis, etc. The application of odorants for behavioral control has not been fully realized yet due to complexity of the mosquito olfactory system. Recent progress in molecular and computational tools has enabled rigorous investigations of the mosquito olfactory system function and has started to reveal how specific receptors contribute to attractive and aversive behaviors. Here we discuss recent advances in linking odors to receptors and in exploiting this knowledge in finding attractants and repellents for mosquitoes.

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Promising Aedes aegypti Repellent Chemotypes Identified through Integrated QSAR, Virtual Screening, Synthesis, and Bioassay

Cited by 46 publications

References 65 publications

Olfactory Mechanisms for Discovery of Odorants to Reduce Insect-Host Contact

Olfactory Mechanisms for Discovery of Odorants to Reduce Insect-Host Contact

Topological QSAR Modelling of Carboxamides Repellent Activity to Aedes Aegypti

Reception of odors and repellents in mosquitoes

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