New antimicrobial agents in the dihydroxanthone series: establishment of structure-activity relationships and standardization
- Authors: Frolova V.V.1, Krishtanova N.A.1, Chernov N.M.1, Gurina S.V.1, Yakovlev I.P.1
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Affiliations:
- Saint Petersburg State Chemical and Pharmaceutical University
- Issue: Vol 27, No 4 (2024)
- Pages: 29-35
- Section: Pharmaceutical chemistry
- URL: https://journals.eco-vector.com/1560-9596/article/view/631163
- DOI: https://doi.org/10.29296/25877313-2024-04-04
- ID: 631163
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Abstract
Introduction. Irrational use of antimicrobial drugs, chemical and biological agents leads to the emergence and spread of resistance in microorganisms. Therefore, there is an increasing need for the search and development of new antimicrobial compounds. Dihydroxanthone derivatives, which have a wide spectrum of action, are one of the promising groups of antimicrobial substances.
New derivatives of 4,4a-dihydroxanthone were obtained at the St. Petersburg State Chemical and Pharmaceutical University (SPCFU) at the Department of Organic Chemistry. Synthetic 4,4a-dihydroxanthones are structurally similar to antimicrobial xanthones of natural origin – fomalevones A and C. Therefore, 4,4a-dihydroxanthones are promising compounds for the creation of new antimicrobial substances.
Purpose of the study. To establish the relationship between the chemical structure of the synthesized dihydroxanthones and their antimicrobial activity and to standardize the active compound.
Materials and methods. 20 new derivatives of 4,4a-dihydroxanthone were synthesized. The structure and identity of the compounds was established using physical and chemical methods of analysis. The antimicrobial activity of these derivatives was studied by double serial dilution method. Quality standards for the most promising compound 5-bromo-7-chloro-4,4-dimethyl-9-oxo-4,4a-dihydroxanthone (a17) were developed.
Results. In preliminary studies, we found that 4,4a-dihydroxanthones synthesized in SPCFU have a pronounced effect against gram-positive bacteria. It was found, that the antibacterial activity of 4,4a-dihydroxanthone derivatives depended on their structure. The presence of substituents with acceptor properties led to an increase in activity, while donor substituents reduced the antimicrobial effect of the compounds. 5-Bromo-7-chloro-4,4-dimethyl-9-oxo-4,4a-dihydroxanthone (a17) turned out to be the most active compound, and we carried out its standardization for some indicators.
Conclusions. During the study of the antimicrobial activity of the synthesized dihydroxanthones, it was found that they are active against gram-positive bacteria. The antibacterial activity of 4,4a-dihydroxanthone derivatives depends on their structure. Among them, the most active compound was identified – leader a17, which has a pronounced antistaphylococcal effect. Its standardization has been carried out for some indicators.
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About the authors
V. V. Frolova
Saint Petersburg State Chemical and Pharmaceutical University
Author for correspondence.
Email: zhilyaeva.valeriya@pharminnotech.com
Assistant, Department of Pharmaceutical Chemistry
Russian Federation, Saint PetersburgN. A. Krishtanova
Saint Petersburg State Chemical and Pharmaceutical University
Email: zhilyaeva.valeriya@pharminnotech.com
Ph.D. (Pharm.)
Russian Federation, Saint PetersburgN. M. Chernov
Saint Petersburg State Chemical and Pharmaceutical University
Email: zhilyaeva.valeriya@pharminnotech.com
Ph.D. (Chem.)
Russian Federation, Saint PetersburgS. V. Gurina
Saint Petersburg State Chemical and Pharmaceutical University
Email: zhilyaeva.valeriya@pharminnotech.com
Ph.D. (Biol.)
Russian Federation, Saint PetersburgI. P. Yakovlev
Saint Petersburg State Chemical and Pharmaceutical University
Email: zhilyaeva.valeriya@pharminnotech.com
Dr.Sc. (Chem.)
Russian Federation, Saint PetersburgReferences
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