Antimicrobial activity study of new quinazolin-4(3h)-ones against Staphylococcus aureus and Streptococcus pneumoniae

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Abstract

Received 08 Jan 2021 Accepted 29 Aug 2021

Quinazolin-4(3H)-one derivatives exhibiting a wide spectrum of a pharmacological activity, represent a promising class of substances used to obtain antibacterial agents, which is especially important in the context of the emergence of pathogenic microorganisms’ resistance to drugs used in medicine. It has been proved that compounds having a naphthyl radical in the molecule, as well as an amide group bound to the benzene ring as quinazolinone substituents, are characterized by a pronounced antimicrobial activity against Staphylococcus aureus and Streptococcus pneumoniae.

The aim of the research is a primary microbiological screening of the in vitro antimicrobial activity of new quinazolin-4(3H)-one derivatives against Staphylococcus aureus and Streptococcus pneumoniae, as well as the assessment of the relationship between the pharmacological effect and the structural transformation of the substance molecule, lipophilicity and the possibility of forming resistance to them.

Materials and methods. The experimental studies have been carried out using well-known nosocomial pathogens of infectious and inflammatory diseases Staphylococcus aureus and Streptococcus pneumoniae by a serial dilution method.

Results. A compound containing a naphthyl radical in its structure, which contributes to an increase in the hydrophobicity of the substance and its solubility in the membrane of a bacterial cell, has a bacteriostatic effect against both Staphylococcus aureus and Streptococcus pneumoniae. A similar pharmacological effect is exhibited by a derivative with an amide group as a substituent of the quinazolinone nucleus linked to a phenyl radical, which probably contributes to an increase in the degree of binding to active sites of enzymes involved in the DNA replication, and protein synthesis. Obviously, the increased lipophilicity, which promotes better binding to the efflux protein, cannot serve as objective characteristics of the emergence possibility of the pathogen’s resistance to this substance.

Conclusion. Among the synthesized compounds, the leading substances that exhibit an antimicrobial activity against Staphylococcus aureus and Streptococcus pneumonia, have been identified. The assessment of the chemical structure made it possible to substantiate their pharmacological action and draw conclusions about the possibility of developing resistance to it in microbial cells.

About the authors

Marina A. Samotrueva

Аstrakhan State Medical University

Email: ms1506@mail.ru
ORCID iD: 0000-0001-5336-4455

Doctor of Sciences (Medicine), Professor, Head of the Department of Pharmacognosy, Pharmaceutical Technology and Biotechnology

Russian Federation, 121, Bakinskaya Str., Astrakhan, Russia, 414000

Alexander A. Ozerov

Volgograd State Medical University; Volgograd Medical Research Center

Email: prof_ozerov@yahoo.com
ORCID iD: 0000-0002-4721-0959

Doctor of Sciences (Chemistry), Professor, Head of the Department of Pharmaceutical and Toxicological Chemistry

Russian Federation, 1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131; 1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

Alla A. Starikova

Аstrakhan State Medical University

Author for correspondence.
Email: alhimik.83@mail.ru
ORCID iD: 0000-0002-5210-5248

Assistant, Department of Chemistry, Faculty of Pharmacy

Russian Federation, 121, Bakinskaya Str., Astrakhan, Russia, 414000

Narmina Mutallimaga-kyzy Gabitova

Astrakhan State Medical University; Scientific Research Institute for the Study of Leprosy

Email: narmina85@inbox.ru
ORCID iD: 0000-0002-3867-8330

Assistant, Department of Pharmacognosy, Pharmaceutical Technology and Biotechnology; Junior Researcher

Russian Federation, 121, Bakinskaya Str., Astrakhan, Russia, 414000; 3, Nikolay Ostrovsky Ave., Astrakhan, Russia, 414057

Daria V. Merezhkina

Volgograd State Medical University

Email: merezhkinad@mail.ru
ORCID iD: 0000-0002-9848-7149

Postgraduate student, Department of Pharmaceutical and Toxicological Chemistry

Russian Federation, 1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

Alexandra A. Tsibizova

Аstrakhan State Medical University

Email: sasha3633@yandex.ru
ORCID iD: 0000-0002-9994-4751

Candidate of Sciences (Pharmacy), Associate Professor, Department of Pharmacognosy, Pharmaceutical Technology and Biotechnology

Russian Federation, 121, Bakinskaya Str., Astrakhan, Russia, 414000

Ivan N. Tyurenkov

Volgograd State Medical University; Volgograd Medical Research Center

Email: fibfuv@mail.ru
ORCID iD: 0000-0001-7574-3923

Doctor of Sciences (Medicine), Professor, Corresponding Member of the Russian Academy of Sciences, Head of the Department of Pharmacology and Pharmacy of the Institute of Continuous Medical and Pharmaceutical Education, the Faculty of Advanced Training of Physicians

Russian Federation, 1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131; 1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

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