AUTHOR=Konečná Klára , Diepoltová Adéla , Holmanová Pavlína , Jand’ourek Ondřej , Vejsová Marcela , Voxová Barbora , Bárta Pavel , Maixnerová Jana , Trejtnar František , Kučerová-Chlupáčová Marta TITLE=Comprehensive insight into anti-staphylococcal and anti-enterococcal action of brominated and chlorinated pyrazine-based chalcones JOURNAL=Frontiers in Microbiology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.912467 DOI=10.3389/fmicb.2022.912467 ISSN=1664-302X ABSTRACT=

The greatest threat and medicinal impact within gram-positive pathogens are posed by two bacterial genera, Staphylococcus and Enterococcus. Chalcones have a wide range of biological activities and are recognized as effective templates in medicinal chemistry. This study provides comprehensive insight into the anti-staphylococcal and anti-enterococcal activities of two recently published brominated and chlorinated pyrazine-based chalcones, CH-0y and CH-0w. Their effects against 4 reference and 12 staphylococcal and enterococcal clinical isolates were evaluated. Bactericidal action, the activity in combination with selected conventional antibiotics, the study of post-antimicrobial effect (PAE, PAE/SME), and in vitro and in vivo toxicity, were included. In CH-0y, anti-staphylococcal activity ranging from MIC = 15.625 to 62.5 μM, and activity against E. faecium from 31.25 to 62.5 μM was determined. In CH-0w, anti-staphylococcal activity ranging from 31.25 to 125 μM, and activity against E. faecium and E. faecalis (62.5 μM) was revealed. Both CH-0y and CH-0w showed bactericidal action, beneficial impact on bacterial growth delay within PAE and PAE/SME studies, and non/low toxicity in vivo. Compared to CH-0w, CH-0y seems to have higher anti-staphylococcal and less toxic potential. In conclusion, chalcones CH-0y and CH-0w could be considered as structural pattern for future adjuvants to selected antibiotic drugs.