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Agricultural Biology  / №6 2016

DERIVATIVES OF 16-MEMBERED MACROCYCLIC LACTONES: ANTIPARASITIC PROPERTIES AND INTERACTION WITH GABAA RECEPTORS (150,00 руб.)

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Первый авторDzhafarov
АвторыVasilevich F.I., Kovalev G.I., Krivonos K.S., Tsepilova I.I., Zavarzin I.V., VasilEva E.V.
Страниц7
ID604356
АннотацияSearching for antiparasitics with a different mode of action than existing drugs, and (or) with the same but much more effective mechanisms is necessary to periodically update the applicable protection chemicals. For the first time we here present data on the biocidal action of new semisynthetic derivatives of avermectin B1 that we have synthetized earlier. These are the 16-membered macrocyclic lactones, the representatives of an important class of anthelmintics. In 2015 S. Omura (Japan) and W. Campbell (USA) who discovered this avermectin group, were awarded the Nobel Prize in physiology and medicine. In our study the oligochaetes Tubificidal tubifex were used as a test-object. The original chemicals and synthetized derivatives tested were avermectin B1 (abamectin), ivermectin, monosaccharide analogues of abamectin and ivermectin, namely abamectin, ivermectin, 5-O-succinyl avermectin B1, methyl ester of 5-O-succinyl avermectin B1, ethyl ester of 5-O-succinyl avermectin B1, diethyl ester of 5,4-di-O-succinyl avermectin B1, ethyl ester of 5-Omalonyl avermectin B1, diethyl ester of 5,4-di-O-dimalonyl avermectin B1, monosaccharide hemisuccinate of avermectin B1 (5-O-succinyl-4´-dezoleandrozyl-4´-hydroxyavermectin B1), ethyl ester of 5-O-succinyl-4-O-chloroacetyl avermectin B1, 5-O-succinyl ivermectin, ethyl ester of 5-O-succinoyl ivermectin, 5,4-di-O-succinyl ivermectin, diethyl ester of 5,4-di-O-succinyl-ivermectin, ethyl ester of 5-O-malonylivermectin, diethyl ester of 5,4-di-O-dimalonyl ivermectin, monoavermectin-5-yl ester of 4-[2-(4-nitrophenyl)-2-oxoethoxy]-4-oxobutanoic acid, monoavermectin-5-yl ester of 4-[2-(4-chlorophenyl)-2-oxoethoxy]-4-oxobutanoic acid, monoavermectin-5-yl ester of 4-[(4-nitrophenyl)-methoxy]-butanoic acid, monoavermectin-5-yl ester of 4-[1-methyl-2-(4-methylphenyl)- 2-oxoethoxy]-4-oxobutanoic acid, monoavermectin-5-yl ester of 4-[2-(4-chlorophenyl)-1-methyl-2oxoethoxy]-4-oxobutanoic acid, monoavermectin-5-yl ester of 4-[3-chloro-1-(4-сhlorbenzoil)-propoxy]-4-oxobutanoic acid, monoavermectin-5-yl ester of 4-{2-[(4-methylphenyl)-amino]-2-oxoethoxy}-4-oxobutanoic acid and monoavermectin-5-yl ester of 4-{2-[(4-bromophenyl)-amino]-2-oxoethoxy}-4-oxobutanoic acid. The acute toxicity (LD50) of the most effective ones, 5-O-succinyl avermectin B1, 5-O-ethylsuccinyl avermectin B1 and 5,4-di-О-ethylsuccinyl avermectin B1, for intraperitoneally challenged white mice was 37.85; 41.37 and 45.82 mg/kg, respectively. We also used membrane preparations of rat brain as in vitro model for screening and studying activity of natural and semi-synthetic avermectins. A radioligand [G-3H]SR 95531 binding assay of avermectin B1, ivermectin, and 5-O-succinyl avermectin B1 interaction with GABA-receptors (the biotargets for these compounds) showed a 30 % increase of maximal inhibition (Imax) of specific binding by hemisuccinate derivative of avermectin B1 when compared to original avermectin B1.
УДК619+61]:615.284:615.45:616-098
DERIVATIVES OF 16-MEMBERED MACROCYCLIC LACTONES: ANTIPARASITIC PROPERTIES AND INTERACTION WITH GABAA RECEPTORS / M.Kh. Dzhafarov [и др.] // Agricultural Biology .— 2016 .— №6 .— С. 102-108 .— URL: https://rucont.ru/efd/604356 (дата обращения: 20.04.2024)

Предпросмотр (выдержки из произведения)

For the first time we here present data on the biocidal action of new semisynthetic derivatives of avermectin B1 that we have synthetized earlier. <...> These are the 16-membered macrocyclic lactones, the representatives of an important class of anthelmintics. <...> In 2015 S. Omura (Japan) and W. Campbell (USA) who discovered this avermectin group, were awarded the Nobel Prize in physiology and medicine. <...> In our study the oligochaetes Tubificidal tubifex were used as a test-object. <...> The original chemicals and synthetized derivatives tested were avermectin B1 (abamectin), ivermectin, monosaccharide analogues of abamectin and ivermectin, namely abamectin, ivermectin, 5-O-succinyl avermectin B1, methyl ester of 5-O-succinyl avermectin B1, ethyl ester of 5-O-succinyl avermectin B1, diethyl ester of 5,4-di-O-succinyl avermectin B1, ethyl ester of 5-Omalonyl avermectin B1, diethyl ester of 5,4-di-O-dimalonyl avermectin B1, monosaccharide hemisuccinate of avermectin B1 (5-O-succinyl-4´-dezoleandrozyl-4´-hydroxyavermectin B1), ethyl ester of 5-O-succinyl-4-O-chloroacetyl avermectin B1, 5-O-succinyl ivermectin, ethyl ester of 5-O-succinoyl ivermectin, 5,4-di-O-succinyl ivermectin, diethyl ester of 5,4-di-O-succinyl-ivermectin, ethyl ester of 5-O-malonylivermectin, diethyl ester of 5,4-di-O-dimalonyl ivermectin, monoavermectin-5-yl ester of 4-[2-(4-nitrophenyl)-2-oxoethoxy]-4-oxobutanoic acid, monoavermectin-5-yl ester of 4-[2-(4-chlorophenyl)-2-oxoethoxy]-4-oxobutanoic acid, monoavermectin-5-yl ester of 4-[(4-nitrophenyl)-methoxy]-butanoic acid, monoavermectin-5-yl ester of 4-[1-methyl-2-(4-methylphenyl)2-oxoethoxy]-4-oxobutanoic acid, monoavermectin-5-yl ester of 4-[2-(4-chlorophenyl)-1-methyl-2oxoethoxy]-4-oxobutanoic acid, monoavermectin-5-yl ester of 4-[3-chloro-1-(4-сhlorbenzoil)-propoxy]-4-oxobutanoic acid, monoavermectin-5-yl ester of 4-{2-[(4-methylphenyl)-amino]-2-oxoethoxy}-4-oxobutanoic acid and monoavermectin-5-yl ester of 4-{2-[(4-bromophenyl)-amino]-2-oxoethoxy}-4-oxobutanoic acid. <...> The acute toxicity (LD50) of the most effective ones, 5-O-succinyl avermectin B1, 5-O-ethylsuccinyl avermectin B1 and 5,4-di-О-ethylsuccinyl avermectin B1, for intraperitoneally challenged white mice was 37.85; 41.37 and 45.82 mg/kg, respectively. <...> We also used membrane preparations of rat brain as in vitro model for screening and studying activity of natural and semi-synthetic avermectins. <...> A radioligand [G-3H]SR 95531 binding assay of avermectin B1, ivermectin, and 5-O-succinyl avermectin B1 <...>