Tautomeric and non-tautomeric N-substituted 2-iminobenzimidazolines as new lead compounds for the design of anti-influenza drugs: An in vitro study

Zarubaev, Vladimir V.; Морковник, А. С.; Диваева, Л. Н.; Karpinskaya, L. A.; Бородкин, Г. С.

doi:10.1016/j.bmc.2016.09.036

Cited by 7 publications

(5 citation statements)

References 35 publications

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“…Опасность гриппозной инфекции, способность вируса гриппа к формированию лекарственноустойчивых штаммов, приводящая к снижению эффективности этиотропной противовирусной терапии, диктует необходимость поиска и разработки новых препаратов, обладающих возможно более высокой эффективнос тью и широким спектром противовирусного действия. Ранее нами были продемонстрированы вирусингибирующие свойства новых производных аминобензимидазолов [18]. В настоящем исследовании представлены данные о противогриппозной активности соединений этой группы в опытах in vivo.…”

Section: Discussionunclassified

“…В опытах по изучению протективной активности производных бензимидазола in vivo были использованы соединения, ране продемонстрировавшие вирусингибирующие свойства в опытах in vitro [18]. Как было показано в ходе экспериментов, инфицирование животных адаптированным вирусом гриппа A/California/7/09 (H1N1)pdm09 приводило к развитию патологического процесса, сопровождающегося смертностью животных начиная с 6 дня после заражения.…”

Section: результатыunclassified

“…Selectivity index in vitro [18] Смертность, % Mortality, % легочной ткани на 5 сут после инфицирования характеризовались поражениями в виде скоплений нейтрофилов и клеточного детрита в просветах крупных бронхов, вирусспецифическим поражением клеток бронхиального эпителия с формированием в них вирусных включений и отторжением пораженных клеток в просвет бронха, интенсивного серозного интерстициального отека, очагов геморрагического отека, нейтрофильной инфильтрации и распада клеток в респираторных отделах, расширением сосудов и спадением альвеол (рис. 3А, III обложка).…”

Section: показатель селективностиunclassified

“…Таким образом, разработка эффективных и доступных средств терапии гриппа, использующих альтернативные мишени и имеющих иные по сравнению с описанными механизмы активности, является актуальной задачей медицинской науки. Ранее нами был продемонстрирован противогриппозный потенциал новых химических соединений группы аминобензими дазолов [18]. Целью настоящего исследования была характеристика противовирусной активности соединений этой группы в опытах in vivo.…”

Section: Introductionunclassified

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Protective Activity of Novel Benzimidazole Derivatives at Experimental Influenza Infection

Zarubaev

Васильева

Есаулкова

et al. 2018

Russian Journal of Infection and Immunity

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Influenza is an acute respiratory viral infection, which represents an important health problem. Every year, influenza causes epidemics and pandemics, leading to increase in morbidity and mortality in all regions of the globe. Due to the segmental organization of the genome and low accuracy of its replication, the influenza virus is capable of escaping the host’s immune response (antigenic drift), as well as the selection of drug-resistant variants. This calls for constant monitoring of the sensitivity of viral isolates to antiviral drugs and the development of new etiotropic antiviral agents that have alternative targets and mechanisms of activity. The purpose of this study was to characterize the new aminobenzimidazole derivatives as protective agents in lethal influenza infection in white mice. The efficacy of the compounds was assessed by their ability to reduce specific mortality of animals in the course of lethal influenza pneumonia caused by the influenza A/Puerto Rico/8/34 (H1N1) irus, increase the life duration of animals, and normalize the morphological structure of lung tissue comparing to the placebo group. For all the compounds studied, a decrease in the specific mortality of animals (from 20 to 60%) has been shown. The reference drug (oseltamivir phosphate) reduced the mortality of mice by 80%. The benzimidazole derivative 2519 demonstrated the highest indices of protective activity, its use reduced the mortality of animals by 60% and increased their mean day of death by 1.6 days in comparison with the control group. Morphological analysis showed that the activity of derivative 2519 was manifested in the normalization of the morphological structure of lung tissue in the course of influenza pneumonia. On day 5 after infection, the cells of the bronchial epithelium looked intact, in contrast to destroyed cells with numerous viral inclusions in control animals. The foci of inflammation themselves occupied a smaller area compared to the control. At the same time, there was no correlation between the previously obtained data on the virus-inhibiting effect of these compounds in vitro and the data obtained in animals. This suggests that despite the presence of direct antiviral activity detected previously in in vitro experiments, the protective properties of the studied aminobenzimidazoles on animals are caused, in addition to the etiotropic effect, by other pathogenetic factors. In conclusion, amino derivatives of benzimidazole should be considered as compounds that are promising for further development and introduction as an anti-influenza agents.

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Section: Discussionunclassified

Section: результатыunclassified

Section: показатель селективностиunclassified

Section: Introductionunclassified

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Protective Activity of Novel Benzimidazole Derivatives at Experimental Influenza Infection

Zarubaev

Васильева

Есаулкова

et al. 2018

Russian Journal of Infection and Immunity

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“…Zarubaev VV et al [11], synthesized a series of 1,3-disubstituted-2-iminobenzimidazolines (Figure 11) and a number of their tautomeric analogs. Synthesized compounds were tested for toxicity to MDCK cells and for inhibiting activity against influenza virus A/California/07/09 (H1N1) pdm09.…”

Section: Figure 10: 2-amino-56-difluorobenzimidazole Nucleosidesmentioning

confidence: 99%

A Review On Substituted Benzimidazoles: Biologically Active Compounds

Madawali¹,

N²,

Kalyane³

et al. 2019

AJPTR

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Benzimidazole is the heterocyclic compound which contains a phenyl ring fused to an imidazole ring, Benzimidazole analogs are of crucial importance because of their different clinical applications and biological activity. Benzimidazoles are known as an optimistic class of bioactive heterocyclic compounds possessing a wide variety of biological activities. Benzimidazole derivatives play an important role in medical field with so many pharmacological activities such as antimicrobial, antiviral, anticancer activity, antioxidant, antiparasitic, antiproliferative, antitumor, anti-HIV, anticonvulsant, antiprotozoal, analgesic and anti-inflammatory, antihypertensive, anticancer, androgen receptor antagonist, vasorelaxant etc. This review is summarized to understand the chemistry of various derivatives of substituted benzimidazoles with their pharmacological activities.

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Design and Synthesis of Some New 3-Oxo/thioxo-1,2,4-triazolo[4,3-a]benzimidazole Derivatives Bearing a 4-Tollyl Sulfonyl Moiety as Antimycobacterial Agents

Bakhotmah

Al-Ahmadi

2019

Polycyclic Aromatic Compounds

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Tautomeric and non-tautomeric N-substituted 2-iminobenzimidazolines as new lead compounds for the design of anti-influenza drugs: An in vitro study

Cited by 7 publications

References 35 publications

Protective Activity of Novel Benzimidazole Derivatives at Experimental Influenza Infection

Protective Activity of Novel Benzimidazole Derivatives at Experimental Influenza Infection

A Review On Substituted Benzimidazoles: Biologically Active Compounds

Design and Synthesis of Some New 3-Oxo/thioxo-1,2,4-triazolo[4,3-a]benzimidazole Derivatives Bearing a 4-Tollyl Sulfonyl Moiety as Antimycobacterial Agents

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