Synthesis and bioassay of improved mosquito repellents predicted from chemical structure

Katritzky, Alan R.; Wang, Zuoquan; Slavov, Svetoslav; Tsikolia, Maia; Dobchev, Dimitar A.; Akhmedov, Novruz G.; Hall, C. Dennis; Bernier, Ulrich R.; Clark, Gary G.; Linthicum, Kenneth J.

doi:10.1073/pnas.0800571105

Cited by 89 publications

(67 citation statements)

References 37 publications

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“…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%

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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Section: Introductionmentioning

confidence: 99%

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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“…1 HNMR spectra of 4a-h showed two signals in the 8.10-7.85 ppm and 12.13-11.15 ppm which are attributed to the N=CH and hydrazone NH protons, respectively. In addition, the N-H peak of indole and urea were observed at 13.98-13.40 ppm and 9.33-7.90 ppm respectively.…”

Section: Resultsmentioning

confidence: 99%

“…All of these diseases can lead to explosive outbreaks in humans which can cause high rates of morbidity and mortality [1][2][3]. These mosquito vectorborne diseases are ecologically sensitive; continue to be endemic in regions with human interactions leading to introductions in new geographical regions and potential epidemics in the future [2].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and larvicidal and adult topical activity of some hydrazidehydrazone derivatives against Aedes aegypti

Akdağ¹,

Koçyığıt‐Kaymakcioğlu²,

Tabanca³

et al. 2014

mpj

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A series of novel hydrazide-hydrazone derivatives were synthesized and evaluated for their larvicidal and adult topical activity against Aedes aegypti. The proposed structures of all the synthesized compounds were confirmed using elemental analysis, UV, IR, 1 H-NMR, 13 C-NMR and mass spectroscopy. Compounds 4a-h were screened in larval bioassays at concentrations of 100, 50 and 25 ppm in a dose dependent manner and data for their mortality was recorded. Among the tested compounds, 1-(4-nitrophenyl)-3-(4-{2-oxo-2-[2-(2-oxo-1,2-dihydro-3H-ylidene)hydrazinyl] ethyl} phenyl)urea (4b) showed noteworthy larvacidal activity against Aedes aegypti. Dose-response data of compound 4b showed LC 50 and LC 90 values of 30.5 (15.4 -22.7) and 95.9 (73.8 -139.4) ppm, respectively. Screening of compounds 4a-h at four doses by topical bioassay indicated a range of activity between 10000 and 1000 ppm.

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“…Three of them (7-9) showed a longer lasting repellent effect than N,N-diethyl-m-toluamide (DEET), which is mostly used as a reference for repellent activity. [25] 3.6 Plant growth regulation Synthesis of 3-methylnonacosanol 10, a plant growth regulator naturally present in Lowsonia inermis L., was performed in a racemic and enantiomeric fashion. The first method comprised a coupling step of undecenyl magnesium bromide with stearyl bromide, and the second method started from a methyl-branched chiron which was also obtained from undecenyl alcohol.…”

Section: Insect-repelling Activitymentioning

confidence: 99%

Undecylenic Acid: A Valuable and Physiologically Active Renewable Building Block from Castor Oil

2009

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A lot of attention is currently being paid to the transition to a biobased economy. In this movement, most efforts concentrate on the development of bioenergy applications including bioethanol, biodiesel, thermochemical conversion of biomass, and others. However, in the energy sector other nonbiomass alternatives are known, whereas no valuable alternatives are available when thinking about chemical building blocks. Therefore, it is also essential to develop new routes for the synthesis of bio-based chemicals and materials derived thereof. Such intermediates can originate either from plants or from animals. Castor oil is a non-edible oil extracted from the seeds of the castor bean plant Ricinus communis (Euphorbiaceae), which grows in tropical and subtropical areas. Globally, around one million tons of castor seeds are produced every year, the leading producing areas being India, PR China, and Brazil.2 10-Undecenoic acid or undecylenic acid is a fatty acid derived from castor oil that, owing to its bifunctional nature, has many possibilities to develop sustainable applications.

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Synthesis and bioassay of improved mosquito repellents predicted from chemical structure

Cited by 89 publications

References 37 publications

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

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

Synthesis and larvicidal and adult topical activity of some hydrazidehydrazone derivatives against Aedes aegypti

Undecylenic Acid: A Valuable and Physiologically Active Renewable Building Block from Castor Oil

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