Antimicrobial and KPC/AmpC inhibitory activity of functionalized benzosiloxaboroles
Krzysztof Durka , Agnieszka Ewa Laudy , Łukasz Charzewski , Mateusz Urban , K. Stępień , Stefan Tyski , K.A. Krzyśko , Sergiusz Luliński
AbstractA series of 22 benzosiloxaboroles, silicon analogues of strong antimicrobial agents - benzoxaboroles, have been synthesized and tested against β-lactamases KPC- and pAmpC-producing strains of Gram-negative rods. Comprehensive structural-property relationship studies supported by molecular modelling as well as biological studies reveal that 6-B(OH)2-substituted derivative 27 strongly inhibits the activity of cephalosporinases (chromosomally encoded AmpC and plasmid encoded CMY-2) and KPC carbapenemases. It also shows strong ability to inhibit growth of the strains producing KPC-3 when combined with meropenem. In addition, halogen-substituted (mono-, di- or tetra-) benzosiloxaboroles demonstrate high antifungal activity (MIC 1.56–6.25 mg/L) against C. tropicalis, C. guilliermondii and S. cerevisiae. The highest activity against pathogenic yeasts (C. albicans, C. krusei and C. parapsilosis - MICs 12.5 mg/L) and against Gram-positive cocci (S. aureus and E. faecalis - 6.25 mg/L and 25 mg/L respectively) was displayed by 6,7-dichloro-substituted benzosiloxaborole. The studied systems exhibit low cytotoxity toward human lung fibroblasts.
|Journal series||European Journal of Medicinal Chemistry, ISSN 0223-5234|
|Publication size in sheets||0.65|
|Keywords in English||BenzosiloxaborolesAntifungal activityAntibacterial activityAmpC/KPC β-lactamase inhibitory activityMolecular dockingEfflux pump|
|Score||= 140.0, 26-06-2020, ArticleFromJournal|
|Publication indicators||= 1; = 0; : 2018 = 1.464; : 2018 = 4.833 (2) - 2018=4.666 (5)|
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