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NEW ANTIMICROBIAL AGENTS IN THE DIHYDROXANTHONE SERIES: ESTABLISHMENT OF STRUCTURE-ACTIVITY RELATIONSHIPS AND STANDARDIZATION
DOI: https://doi.org/10.29296/25877313-2024-04-04
Issue:
4
Year:
2024
Introduction. Irrational use of antimicrobial drugs, chemical and biological agents leads to the emergence and spread of resistance in microorgan-isms. 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 ac-tivity 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 estab-lished 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.
Keywords:
antimicrobial activity
antimicrobial resistance
antistaphylococcal effect
dihydroxanthones
standardization
quality standards
structure-activity.
References:
- Strategija preduprezhdenija rasprostranenija antimikrobnoj rezistentnosti v Rossijskoj Federacii na period do 2030 goda.
- Vsemirnaja organizacija zdravoohranenija. Rezhim dostupa: http://www.who.int/ru.
- Eltamany E.E., Abdelmohsen U.R., Ibrahim A.K., et al. New antibacterial xanthone from the marine sponge-derived Micrococcus sp. EG45. Bioorganic and Medicinal Chemistry Letters. 2014; 24(21): 4939–4942; https://doi.org/10.1016/j.bmcl.2014.09.040.
- Pinto M.M.M., Sousa M.E., Nascimento M.S.J. Xanthone Derivatives: New Insights in Biological Activities. Current Medicinal Chemistry. 2005; 12(21): 2517–2538; https://doi.org/10.2174/092986705774370691.
- Chernov N.M., Shutov R.V., Jakovlev I.P. Digidro-ksantony: himija i biologicheskaja aktivnost': monogr. 2019; 154 s.
- Frolova V.V., Gurina S.V., Chernov N.M., Jakovlev I.P. Sravnitel'naja ocenka protivomikrobnoj aktivnosti soedinenij rjada ksantonov. Bakteriologija. 2019; 4(2): 65–66.
- Shim S.H., Baltrusaitis J., Gloer J.B., Wicklow D.T. Pho-malevones A−C: Dimeric and Pseudodimeric Polyketides from a Fungicolous Hawaiian Isolate of Phoma sp. (Cucurbitariaceae). Joutnal of Natural Products. 2011; 74(3): 395–401. DOI: 10.1021/np100791b.
- Frolova V.V., Gurina S.V., Chernov N.M., Jakovlev I.P. 4,4a-digidroksantony kak perspektivnye soedinenija dlja sozdanija novyh antimikrobnyh preparatov. Anti-biotiki i himioterapija. 2019; 64(11-12): 3–7.
- Chernov N.M., Shutov R.V., Sharoyko V.V., et al. Synthetic Route to 4,4a- and 3,4-Dihydroxanthones through [4+2] Cycloaddition and Base-Assisted Sigmatropic Rearrangement. European Journal of Organic Chemistry. 2017; 19: 2836–2841; https://doi.org/10.1002/ejoc.201700310.
- Gosudarstvennoj Farmakopeej RF XV izd. Tom [Jelektronnoe izdanie]. Rezhim dostupa: https://pharmacopoeia.regmed.ru/pharmacopoeia/izdanie-15/.
- Rukovodstvo po provedeniju doklinicheskih issledovanij lekarstvennyh sredstv. Chast' pervaja. M.: Grif i K. 2012. 944 s.
- Frolova V.V., Chernov N.M., Ivkin D.Ju., i dr. Opre-delenie vozmozhnoj misheni dejstvija 4,4a-digidroksantonov v bakterial'nyh kletkah. Zhurnal mikrobio-logii, jepi-demiologii i immunobiologii. 2021; 98(5): 558–566; https://doi.org/10.36233/0372-9311-118.
- Frolova V.V., Gurina S.V., Chernov N.M., Jakovlev I.P. Vzaimosvjaz' mezhdu stroeniem novyh proizvodnyh digidroksantona i ih protivomikrobnoj aktivnost'ju. Mate-rialy Mezhdunarodnoj konferencii, posvjashhennoj 60-letiju farmacevticheskogo fakul'teta uchrezhdenija obrazovanija «Vitebskij gosudarstvennyj ordena Druzhby narodov medicinskij universitet» (Vitebsk, 31 okt. 2019 g.). Pod red. A. T. Shhastnogo. Vitebsk: VGMU. 2019: 30–33.