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


A 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.
Author Krzysztof Durka (FC / DPC)
Krzysztof Durka,,
- Department Of Physical Chemistry
, Agnieszka Ewa Laudy - [Medical University of Warsaw]
Agnieszka Ewa Laudy,,
, Łukasz Charzewski - [University of Warsaw (UW)]
Łukasz Charzewski,,
- Uniwersytet Warszawski
, Mateusz Urban (FC / DPC)
Mateusz Urban,,
- Department Of Physical Chemistry
, K. Stępień - [Medical University of Warsaw]
K. Stępień,,
, Stefan Tyski - [Medical University of Warsaw]
Stefan Tyski,,
, K.A. Krzyśko - [University of Warsaw (UW)]
K.A. Krzyśko,,
- Uniwersytet Warszawski
, Sergiusz Luliński (FC / DPC)
Sergiusz Luliński,,
- Department Of Physical Chemistry
Journal seriesEuropean Journal of Medicinal Chemistry, ISSN 0223-5234
Issue year2019
Publication size in sheets0.65
Keywords in EnglishBenzosiloxaborolesAntifungal activityAntibacterial activityAmpC/KPC β-lactamase inhibitory activityMolecular dockingEfflux pump
ASJC Classification1605 Organic Chemistry
Languageen angielski
1-s2.0-S0223523419302466-main.pdf 1.48 MB
Score (nominal)140
Score sourcejournalList
ScoreMinisterial score = 140.0, 26-06-2020, ArticleFromJournal
Publication indicators Scopus Citations = 1; WoS Citations = 0; Scopus SNIP (Source Normalised Impact per Paper): 2018 = 1.464; WoS Impact Factor: 2018 = 4.833 (2) - 2018=4.666 (5)
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