Development of a Promising Method for Producing Oligomeric Mixture of Branched Alkylene Guanidines to Improve Substance Quality and Evaluate Their Antiviral Activity against SARS-CoV-2.

Alexander Herbst,Lasse Greiner,Sergei V Beliakov,Viktor P Volok,Diana A Akhmedova,Liubov I Kozlovskaya,Stanislav A Kedik,Denis O Shatalov,Dmitrii S Minenkov,Anna V Aydakova,Ivan S Ivanov

doi:10.3390/molecules26113472

Abstract

This paper reports the synthesis of branched alkylene guanidines using microfluidic technologies. We describe the preparation of guanidine derivatives at lower temperatures, and with significantly less time than that required in the previously applicable method. Furthermore, the use of microfluidics allows the attainment of high-purity products with a low residual monomer content, which can expand the range of applications of this class of compounds. For all the samples obtained, the molecular-weight characteristics are calculated, based on which the optimal condensation conditions are established. Additionally, in this work, the antiviral activity of the alkylene guanidine salt against the SARS-CoV-2 virus is confirmed.

Highlights

Diseases caused by various infections are considered to be among the most common pathologies that a person acquires in the modern world
The optimism associated with the synthesis of a new class of drugs at the beginning and middle of the 20th century was extinguished by the development of antimicrobial resistance (AMR) due to the overuse of these drugs
Based on the results of this work, we can conclude that the principles of microfluidics can be successfully applied to guanidine-type antiseptic production

Summary

Introduction

Diseases caused by various infections are considered to be among the most common pathologies that a person acquires in the modern world. At least 50,000 people die from infectious diseases caused by drug-resistant microorganisms in Europe and the USA, and in developing countries, this number reaches hundreds of thousands [1]. These infectious diseases include pneumonia, tuberculosis, human immunodeficiency virus, malaria, oncology, against which antibiotics play a decisive role, in chemotherapy and surgical procedures in general (e.g., organ transplantation and caesarean section). According to experts [3], in the chemotherapy of infectious diseases, it is permissible to use several AMAs, e.g., a combination of antibiotics and antiseptics This is because the microbial association has different levels of sensitivity, and the combination of AMAs enables the prevention or retardation of the AMR formation in pathogens and enhances their inactivating effect based on the synergistic activity of the active substances

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Conclusion