antibioticsАнтибиотики и ХимиотерапияAntibiot Khimioter = Antibiotics and Chemotherapy0235-2990ООО «Издательство ОКИ»10.37489/0235-2990-2024-69-1-2-15-22EETRYBantibiotics-1104Research ArticleЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯEXPERIMENTAL STUDIESАнтибактериальная и антибиоплёночная активность N-арилпроизводных бензимидазола, бензотриазола и их гибридовAntibacterial and antibiofilm activity of N-aryl derivatives of benzimidazole, benzotriazole and their hybridshttps://orcid.org/0000-0002-4610-9744БегуновР. С.BegunovR.  S.

Бегунов Роман Сергеевич — к. х. н., доцент; доцент Факультета биологии и экологии

ул. Советская, д. 14, ЯГУ им. П. Г. Демидова, г. Ярославль, 150003

Roman S. Begunov — Ph. D. in Chemistry, Associate Professor; Associate Professor of the Faculty of Biology and Ecology

14 Sovetskaya st., P. G. Demidov Yaroslavl State University, Yaroslavl, 150003 

begunov@bio.uniyar.ac.ruhttps://orcid.org/0000-0001-9109-023XЕгоровД. О.EgorovD. O.

Егоров Дмитрий Олегович — аспирант, Факультет биологии и экологии 

Ярославль

Dmitry O. Egorov — Laboratory assistant, Postgraduate student, Faculty of Biology and Ecology

Yaroslavl

ЧетвертаковаА. В.ChetvertakovaA. V.

Четвертакова Анна Васильевна — студент, Факультет биологии и экологии

Ярославль

Anna V. Chetvertakova — Student, Faculty of Biology and Ecology

Yaroslavl

ХлопотининА. И.KhlopotininA. I.

Хлопотинин Александр Игоревич — аспирант, Факультет биологии и экологии 

Ярославль

Alexander I. Khlopotinin — Laboratory assistant, Postgraduate student, Faculty of Biology and Ecology

Yaroslavl

   

СавинаЛ. И.SavinaL. I.

Савина Луиза Ильинична — студент, Факультет биологии и экологии

Ярославль

Luisa I. Savina — Student, Faculty of Biology and Ecology

Yaroslavl

   

ВиноградоваВ. А.VinogradovaV. A.

Виноградова Вероника Алексеевна — студент, Факультет биологии и экологии 

Ярославль

Veronika A. Vinogradova — Student, Faculty of Biology and Ecology

Yaroslavl

   

ЗубишинаА. А.ZubishinaA. A.

Зубишина Алла Александровна — к. б. н., доцент Факультета биологии и экологии

AuthorID: 91911

Ярославль

Alla A. Zubishina — Ph. D. in Biology, Associate Professor, Faculty of Biology and Ecology

Yaroslavl

   

Ярославский государственный университет им. П. Г. ДемидоваРоссияP. G. Demidov Yaroslavl State UniversityRussian Federation202415042024691-21522Copyright © Бегунов Р.С., Егоров Д.О., Четвертакова А.В., Хлопотинин А.И., Савина Л.И., Виноградова В.А., Зубишина А.А., 20242024Бегунов Р.С., Егоров Д.О., Четвертакова А.В., Хлопотинин А.И., Савина Л.И., Виноградова В.А., Зубишина А.А.Begunov R.S., Egorov D.O., Chetvertakova A.V., Khlopotinin A.I., Savina L.I., Vinogradova V.A., Zubishina A.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.antibiotics-chemotherapy.ru/jour/article/view/1104Актуальность

Актуальность. Рост числа штаммов бактерий с множественной лекарственной устойчивостью, вызывающих трудно излечимые инфекционные заболевания, стал одной из серьёзных проблем XXI века. Поэтому в настоящее время существует острая потребность в новых препаратах, действующих против резистентных микроорганизмов.

Цель

Цель. Сравнение способности ингибировать рост и образование биоплёнок грамположительных Bacillus subtilis и грамотрицательных Pseudomonas aeruginosa, Escherichia coli бактерий соединениями, содержащими один или два фармакофорных полиазагетероцикла. Методы. Антибактериальную активность полиазагетероциклов оценивали методом серийных разведений в концентрации 31,25–1000 мкг/мл в отношении планктонных форм и биоплёнок Pseudomonas aeruginosa PAO1, Escherichia coli AB1157, Bacillus subtilis BKM B-407. Минимальная подавляющая концентрация (МПК₅₀) была определена как концентрация тестируемого соединения, подавляющая рост бактерий после 24 ч инкубации на 50 %. В качестве тестируемых соединений использовали производные трифторметилбензола, содержащие бензимидазольный и/или бензотриазольный циклы.

Результаты

Результаты. Изучена антибактериальная и антибиоплёночная активность N-арилпроизводных бензимидазола, бензотриазола и гибридов на их основе. Cоединения, содержащие бензимидазольный цикл, обладали большим антибактериальным эффектом по сравнению с аналогами с бензотриазольным фрагментом. Новые гибридные материалы способны ингибировать факторы патогенности бактерий, такие как способность образования биоплёнок (биоплёнкообразование). Наличие метильного и трифторметильного заместителя во втором положении бензимидазола усиливало антибиоплёночную активность гибридной молекулы.

Заключение

Заключение. Наличие в соединении бензимидазольного цикла является обязательным условием проявления высокой антимикробной активности. Наблюдался синергизм действия двух азагетероциклов — бензимидазольного и бензотриазольного в гибридном соединении на биоплёнкообразование бактерий, являющееся важной детерминантой вирулентности. Полученные гибридные вещества являются перспективными соединениями для разработки новых антибактериальных препаратов в отношении резистентных бактерий

Background

Background. The growing number of multidrug-resistant bacterial strains causing intractable infectious diseases has become one of the serious problems of the 21st century. Therefore, new drugs that act against resistant microorganisms are urgently needed.

The aim of the study

The aim of the study. Comparison of the ability to inhibit the growth and formation of biofilms of Gram-positive Bacillus subtilis and Gram-negative Pseudomonas aeruginosa, Escherichia coli bacteria with compounds containing one or two pharmacophore polyazaheterocycles.

Material and methods

Material and methods. The antibacterial activity of polyazaheterocycles was evaluated by serial dilution at a concentration of 31.25–1000 µg/ml against planktonic forms and biofilms of Pseudomonas aeruginosa PAO1, Escherichia coli AB1157, and Bacillus subtilis BKM B-407. The minimum inhibitory concentration (MIC₅₀) was defined as the concentration of the test compound that suppresses bacterial growth by 50% after 24 hours of incubation. Trifluoromethylbenzene derivatives containing benzimidazole and/or benzotriazole cycles were used as test compounds.

Results

Results. The antibacterial and antibiofilm activity of N-aryl derivatives of benzimidazole, benzotriazole and hybrids based on them were studied. Compounds containing the benzimidazole cycle had a greater antibacterial effect compared to analogues with a benzotriazole fragment. New hybrid materials are capable of inhibiting bacterial pathogenicity factors, such as the ability to form biofilms. The presence of a methyl and trifluoromethyl substituent in the second position of benzimidazole enhanced the antibiofilm activity of the hybrid molecule.

Conclusion

Conclusion. The presence of a benzimidazole cycle in the compound is a prerequisite for the manifestation of high antimicrobial activity. The synergism of the action of two azaheterocycles — benzimidazole and benzotriazole — in a hybrid compound on bacterial biofilm formation, which is an important virulence determinant, was observed. The resulting hybrid substances are promising compounds for the development of new antibacterial drugs against resistant bacteria.

   

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The authors declare that there are no conflicts of interest present.