Antiprotozoal activity of halogen-derived imidazole systems

УДК 619:616.993.192
DOI 10.33861/2071-8020-2022-5-28-31

Zubenko A.A., Fetisov L.N., Svyatogorova A.E., Kononenko K.N., Klimenko A.I.

Summary. The present work includes methods of modification and preparation of new halogen derivatives of imidazole systems. Our research has established the level of antiprotozoal activity of newly synthesized halogenated derivatives of imidazole systems. Compounds 1-8, 13-17 synthesized by the reaction of 4,5 dichlorimidazoles with corresponding alkyl halides in an alkaline medium exhibit protistocidal activity at the level of 62,5 to 15,6 mcg/ml. This level is equal to or exceeds the activity level of the comparison drugs toltrazuril and chloroquil. In the synthesis of pyridine derivative 11, 2-chloro-3-nitro-pyridine and 4,5-dichlorimidazole were used, which were boiled in dimethylformamide in the presence of one base equivalent. The level of protistocidal activity of this compound also turned out to be significant and amounted to 31,25 mcg/ml, which is twice as high as the activity of toltrazuril. A similar technique was used in the synthesis of structure 9 using 1-(2-hydroxyethyl)-4,5-dichlorimidazole and 2-chloro-3-nitropyridine. The activity of this compound was equal to that of toltrazuril. The derivative of 2-bromo-4,5-dichlorimidazole (15) has an activity at the level of 0,48 mcg /ml, exceeding the activity of comparison drugs. Product 17 was obtained by alkylation of 4,5-dichlorimidazole with n-nitrobenzyl chloride followed by reduction of the nitro group. Ketone 10 was synthesized by methylation of 2-benzoyl-4,5-dichlorimidazole with dimethyl sulfate in an alkaline medium. Compound 16 was obtained by alkylation of 2,4,5-tribromimidazole with chloroacetonitrile in an alkaline medium. The compound 18 is a benzimidazole derivative and is described by us in RF Patent №2477129. These groups of compounds showed high biological activity against the Colpoda steinii test culture (from 500 mcg/ml to 0.24 mcg/ml). The obtained halimidazoles can be used for extended toxicological and pharmacological studies in order to develop methods of treating animals with protozoal diseases.

Keywords: halogen derivatives of imidazole systems, synthesis methods, Colpoda steinii protozoa, level of antiprotozoal activity depending on the structure of synthesized compounds

References:

1. Aleksandrova E.V. Kravchenko A.N., Kochergin P.M. Metody sinteza galogenimidazolov [Methods for the synthesis of haloimidazoles]. - Chemistry of Heterocyclic Compounds. - Riga, 2010 (11). - pp. 1603-1629.

2. Mashkovskiy M.D. Lekarstvennye sredstva [Pharmaceuticals]. - Moscow, 2005. - p. 444.

3. Fetisov L.N., Zubenko A.A., Bodryakov A.N., Bodryakova M.A. Izyskanie protistotsidnykh sredstv [Finding protistocidal agents]. - Issues of regulatory and legal regulation in veterinary medicine. - Saint-Petersburg, 2012 (4/1). - pp. 70-72 4-10. Vide supra.

Author information:

Zubenko Aleksandr A., D.Sc. in Biology, chief scientific researcher of the North Caucasian Zonal Scientific-Research Veterinary Institute - branch of the Federal Rostov Agrarian Scientific Center; 0, Rostovskoe hgw., Novocherkassk, Rostov region, 346421; phone: 8-928-6049743; e-mail: alexsandrzubenko@yandex.ru.

Fetisov Leonid N., Ph.D. in Veterinary Medicine, leading scientific researcher of the North Caucasian Zonal Scientific-Research Veterinary Institute -branch of the Federal Rostov Agrarian Scientific Center; 0, Rostovskoe hgw., Novocherkassk, Rostov region, 346421; phone: 8-908-1978224; e-mail: fetisoff.leonid2018@yandex.ru.

Kononenko Kristina N., scientific researcher of the North Caucasian Zonal Scientific-Research Veterinary Institute - branch of the Federal Rostov Agrarian Scientific Center; 0, Rostovskoe hgw., Novocherkassk, Rostov region, 346421; phone: 8-918-5943886; e-mail: velikayakrista@mail.ru.

Klimenko Aleksandr I., Academician of the Russian Academy of Sciences, D.Sc. in Agriculture, Professor, Director of the Federal Rostov Agrarian Scientific Center; 1, Institutskaya st., Rassvet vllg., Aksay district, Rostov region, 346735; e-mail: dzni@mail.ru.

Responsible for correspondence with the editorial board: Svyatogorova Aleksandra E., junior scientific researcher of the North Caucasian Zonal Scientific-Research Veterinary Institute - branch of the Federal Rostov Agrarian Scientific Center; 0, Rostovskoe hgw., Novocherkassk, Rostov region, 346421; phone: 8-988-9525755; e-mail: sviatogorova.a@yandex.ru.