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Assessing the anthelmintic activity of pyrazole-5-carboxamide derivatives against Haemonchus contortus
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نویسنده
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jiao y. ,preston s. ,song h. ,jabbar a. ,liu y. ,baell j. ,hofmann a. ,hutchinson d. ,wang t. ,koehler a.v. ,fisher g.m. ,andrews k.t. ,laleu b. ,palmer m.j. ,burrows j.n. ,wells t.n.c. ,wang q. ,gasser r.b.
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منبع
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parasites and vectors - 2017 - دوره : 10 - شماره : 1
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چکیده
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Background: in this study,we tested five series of pyrazole-5-carboxamide compounds (n = 55) for activity against parasitic stages of the nematode haemonchus contortus (barber’s pole worm),one of the most pathogenic parasites of ruminants. methods: in an optimised,whole-organism screening assay,using exsheathed third-stage (xl3) and fourth-stage (l4) larvae,we measured the inhibition of larval motility and development of h. contortus. results: amongst the 55 compounds,we identified two compounds (designated a-15 and a-17) that reproducibly inhibit xl3 motility as well as l4 motility and development,with ic50 values ranging between ~3.4 and 55.6 μm. we studied the effect of these two ‘hit’ compounds on mitochondrial function by measuring oxygen consumption. this assessment showed that xl3s exposed to each of these compounds consumed significantly less oxygen and had less mitochondrial activity than untreated xl3s,which was consistent with specific inhibition of complex i of the respiratory electron transport chain in arthropods. conclusions: the present findings provide a sound basis for future work,aimed at identifying the targets of compounds a-15 and a-17 and establishing the modes of action of these chemicals in h. contortus. © 2017 the author(s).
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کلیدواژه
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Haemonchus contortus; Mitochondrial respiratory chain; Phenotypic screening; Synthetic pyrazole-5-carboxamide derivatives; Tolfenpyrad
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آدرس
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faculty of veterinary and agricultural sciences,the university of melbourne,parkville,vic 3010, Australia, faculty of veterinary and agricultural sciences,the university of melbourne,parkville,vic 3010,australia,faculty of science and technology,federation university,ballarat,vic 3350, Australia, state key laboratory of elemento-organic chemistry,research institute of elemento-organic chemistry,nankai university,tianjin,300071, China, faculty of veterinary and agricultural sciences,the university of melbourne,parkville,vic 3010, Australia, state key laboratory of elemento-organic chemistry,research institute of elemento-organic chemistry,nankai university,tianjin,300071, China, medicinal chemistry,monash university institute of pharmaceutical sciences (mips),monash university,parkville,vic 3052, Australia, griffith institute for drug discovery,griffith university,don young road,nathan,qld 4111, Australia, drug discovery biology,monash university institute of pharmaceutical sciences (mips),monash university,parkville,vic 3052, Australia, faculty of veterinary and agricultural sciences,the university of melbourne,parkville,vic 3010, Australia, faculty of veterinary and agricultural sciences,the university of melbourne,parkville,vic 3010, Australia, griffith institute for drug discovery,griffith university,don young road,nathan,qld 4111, Australia, griffith institute for drug discovery,griffith university,don young road,nathan,qld 4111, Australia, medicines for malaria venture (mmv),route de pré-bois 20,geneva,ch-1215, Switzerland, medicines for malaria venture (mmv),route de pré-bois 20,geneva,ch-1215, Switzerland, medicines for malaria venture (mmv),route de pré-bois 20,geneva,ch-1215, Switzerland, medicines for malaria venture (mmv),route de pré-bois 20,geneva,ch-1215, Switzerland, state key laboratory of elemento-organic chemistry,research institute of elemento-organic chemistry,nankai university,tianjin,300071, China, faculty of veterinary and agricultural sciences,the university of melbourne,parkville,vic 3010,australia,state key laboratory of agricultural microbiology,college of veterinary medicine,huazhong agricultural university,wuhan,hubei 430070, China
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Authors
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