Carboxamides Combining Favorable Olfactory Properties with Insect Repellency

Gaudin, Jean‐Marc; Lander, Thierry; Nikolaenko, Olga

doi:10.1002/cbdv.200890058

Cited by 10 publications

(16 citation statements)

References 6 publications

(2 reference statements)

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“…Cooling, the prominent sensory property of menthol, is mediated by the TRPM8 channel (Voets et al, 2004 ). The WS-23 compound also stimulates the TRPM8 channel and has been reported to have virtually no taste or odor (Gaudin et al, 2008 ). We nevertheless used an odor habituation test (Inagaki et al, 2010 ) to examine whether WS-23 has an odor that can be detected by rats.…”

Section: Resultsmentioning

confidence: 99%

Menthol facilitates the intravenous self-administration of nicotine in rats

Wang

Chen

2014

Front. Behav. Neurosci.

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Menthol is preferred by~25% of smokers and is the most common flavoring additive in tobacco and electronic cigarettes. Although some clinical studies have suggested that menthol facilitates the initiation of smoking and enhances the dependence on nicotine, many controversies remain. Using licking as the operant behavior, we found that adolescent rats self-administering nicotine (30 µg/kg/infusion, free base, i.v.) with contingent oral menthol (60 µl, 0.01% w/v) obtained significantly more infusions than rats receiving a vehicle cue or rats self-administering i.v. saline with a menthol cue. Rats yoked to their menthol-nicotine masters emitted significantly fewer licks on the active spouts, indicating that contingent pairing between nicotine and menthol is required for sustained nicotine intake. Rats that self-administered nicotine with a menthol cue also exhibited a long-lasting extinction burst and robust reinstatement behavior, neither of which were observed in rats that self-administered saline with a menthol cue. The cooling sensation of menthol is induced by activating the transient receptor potential M8 (TRPM8) channel. When WS-23, an odorless agonist of the TRPM8 channel, was used as a contingent cue for nicotine, the rats obtained a similar number of nicotine infusions as the rats that were provided a menthol cue and exhibited a strong preference for the active spout. In contrast, highly appetitive taste and odor cues failed to support nicotine self-administration. These data indicated that menthol, likely by inducing a cooling sensation, becomes a potent conditioned reinforcer when it is contingently delivered with nicotine. Together, these results provide a key behavioral mechanism by which menthol promotes the use of tobacco products or electronic cigarettes.

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Section: Resultsmentioning

confidence: 99%

Menthol facilitates the intravenous self-administration of nicotine in rats

Wang

Chen

2014

Front. Behav. Neurosci.

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“…These derivatives have been characterized as physiologically relevant lead compounds with repellent properties [24,26,27]. To evaluate the accuracy of our methodology, DEET and 1-NPN were used as bench-mark molecules.…”

Section: Modeling Of Structurally Related Repellentsmentioning

confidence: 99%

“…Additionally, we have investigated 12 carboxamides proposed by Gaudin et al [24]. Six of them have very promising olfactory profiles (Table 3; a/a 13-18), four share improved repellency properties against three breeds of cockroach (Table 3; a/a 19-22) and two combine both characteristics (Table 3, a/a 23, 24).…”

Section: Modeling Of Structurally Related Repellentsmentioning

confidence: 99%

“…Six of them have very promising olfactory profiles (Table 3; a/a 13-18), four share improved repellency properties against three breeds of cockroach (Table 3; a/a 19-22) and two combine both characteristics (Table 3, a/a 23, 24). The remaining five ligands (Table 3; a/a 25-29) are simple or naturally occurring carboxamides known to be active against insects [24].…”

Section: Modeling Of Structurally Related Repellentsmentioning

confidence: 99%

“…To date, a number of QSAR studies of carboxamides [24][25][26] and piperidines [27] have been employed for the development of more efficient and environmentally friendly repellents and insecticides. However, in the absence of structural data on repellents in complex with a macromolecular target, a rational structure-based design approach by necessity has yet to be realized.…”

Section: Introductionmentioning

confidence: 99%

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Anopheles gambiae odorant binding protein crystal complex with the synthetic repellent DEET: implications for structure-based design of novel mosquito repellents

Tsitsanou

Thireou

Drakou

et al. 2011

Cell. Mol. Life Sci.

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Insect odorant binding proteins (OBPs) are the first components of the olfactory system to encounter and bind attractant and repellent odors emanating from various sources for presentation to olfactory receptors, which trigger relevant signal transduction cascades culminating in specific physiological and behavioral responses. For disease vectors, particularly hematophagous mosquitoes, repellents represent important defenses against parasitic diseases because they effect a reduction in the rate of contact between the vectors and humans. OBPs are targets for structure-based rational approaches for the discovery of new repellent or other olfaction inhibitory compounds with desirable features. Thus, a study was conducted to characterize the high resolution crystal structure of an OBP of Anopheles gambiae, the African malaria mosquito vector, in complex with N,N-diethyl-m-toluamide (DEET), one of the most effective repellents that has been in worldwide use for six decades. We found that DEET binds at the edge of a long hydrophobic tunnel by exploiting numerous non-polar interactions and one hydrogen bond, which is perceived to be critical for DEET's recognition. Based on the experimentally determined affinity of AgamOBP1 for DEET (K (d) of 31.3 μΜ) and our structural data, we modeled the interactions for this protein with 29 promising leads reported in the literature to have significant repellent activities, and carried out fluorescence binding studies with four highly ranked ligands. Our experimental results confirmed the modeling predictions indicating that structure-based modeling could facilitate the design of novel repellents with enhanced binding affinity and selectivity.

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Mild and Low‐Pressure fac‐Ir(ppy)₃‐Mediated Radical Aminocarbonylation of Unactivated Alkyl Iodides through Visible‐Light Photoredox Catalysis

Chow

Stevens

Åkerbladh

et al. 2016

Chemistry A European J

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A novel, mild and facile preparation of alkyl amides from unactivated alkyl iodides employing a fac-Ir(ppy)3 -catalyzed radical aminocarbonylation protocol has been developed. Using a two-chambered system, alkyl iodides, fac-Ir(ppy)3 , amines, reductants, and CO gas (released ex situ from Mo(CO)6 ), were combined and subjected to an initial radical reductive dehalogenation generating alkyl radicals, and a subsequent aminocarbonylation with amines affording a wide range of alkyl amides in moderate to excellent yields.

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Carboxamides Combining Favorable Olfactory Properties with Insect Repellency

Cited by 10 publications

References 6 publications

Menthol facilitates the intravenous self-administration of nicotine in rats

Menthol facilitates the intravenous self-administration of nicotine in rats

Anopheles gambiae odorant binding protein crystal complex with the synthetic repellent DEET: implications for structure-based design of novel mosquito repellents

Mild and Low‐Pressure fac‐Ir(ppy)₃‐Mediated Radical Aminocarbonylation of Unactivated Alkyl Iodides through Visible‐Light Photoredox Catalysis

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Carboxamides Combining Favorable Olfactory Properties with Insect Repellency

Cited by 10 publications

References 6 publications

Menthol facilitates the intravenous self-administration of nicotine in rats

Menthol facilitates the intravenous self-administration of nicotine in rats

Anopheles gambiae odorant binding protein crystal complex with the synthetic repellent DEET: implications for structure-based design of novel mosquito repellents

Mild and Low‐Pressure fac‐Ir(ppy)3‐Mediated Radical Aminocarbonylation of Unactivated Alkyl Iodides through Visible‐Light Photoredox Catalysis

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Product

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Mild and Low‐Pressure fac‐Ir(ppy)₃‐Mediated Radical Aminocarbonylation of Unactivated Alkyl Iodides through Visible‐Light Photoredox Catalysis