Ізооксазоловмісні сульфонаміди як нові антибактеріальні агенти: in silico дослідження, синтез та in vitro оцінка

• Date: 2022
• Main Authors: Hodyna, Diana M., Pavliuk, Oleksandr V., Baran, Maria M., Yevdokymenko, Vitaliy O., Kovalishyn, Vasyl V., Metelytsia, Larysa O.
• Format: Article
• Language: English
• Published: V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine 2022
• Subjects: QSAR; антибактеріальна активність; ізооксазол; сульфаніламід; токсичність
• Online Access: https://bioorganica.com.ua/index.php/journal/article/view/32
• Journal Title: Ukrainica Bioorganica Acta

The QSAR models previously created by the OCHEM web platform were used for the research and design of novel isoxazole derivatives as antimicrobial agents. Based on the created virtual set of promising isoxazole derivatives, a number of potential antibacterial agents were selected for synthesis and further research. A convenient synthetic sequence for obtaining initial isoxazole-containing sulfonylamides and preparative methods for the synthesis of target sulfonylamides of the isoxazole series, in particular, using ring-closing metathesis reactions, were worked out. The results of in vitro antimicrobial activity evaluation of synthesized compounds with predicted high activity showed that a series of isoxazole-containing sulfonylamides are promising antimicrobial agents with a wide spectrum of antibacterial action, especially against multidrug-resistant E. coli, A. baumannii and S. aureus bacterial pathogens. In vivo assessment of the acute toxicity of the studied compounds on the D. magna as a known biosensor proved that most of the studied isoxazole derivatives can be attributed to the class of slightly toxic substances according to the classification developed by Passino and Smith for hydrobionts