Issue 41, 2021

Development of structurally extended benzosiloxaboroles – synthesis and in vitro biological evaluation

Abstract

The synthesis of potassium 6-hydroxy-7-chloro-1,1-dimethyl-3,3-difluorobenzo-1,2,3-siloxaborolate 5b from readily available 4-bromo-2-chlorophenol was developed. This compound proved useful in various derivatizations resulting in a wide range of O-functionalized benzosiloxaboroles. Reactions of 5b with selected substituted benzoyl chlorides gave rise to a series of respective derivatives with 6-benzoate side groups attached to the benzosiloxaborole core. Furthermore, treatment of 5b with substituted benzenesufonyl chlorides afforded several benzosiloxaboroles bearing functionalized benzenesulfonate moieties at the 6 position. The synthesis of related chloropyridine-2-yloxy substituted benzosiloxaboroles was accomplished by a standard approach involving silylation/boronation of appropriate heterodiaryl ethers. Investigation of biological activity of obtained compounds revealed that some benzoate and most benzenesulfonate derivatives exhibit high activity against Gram-positive cocci such as methicillin-sensitive Staphylococcus aureus ATCC 6538P as well as methicillin-resistant S. aureus ATCC 43300 with the MIC values in the range of 0.39–3.12 mg L−1. Some benzenesulfonate derivatives showed also potent activity against Enterococcus faecalis ATCC 29212 and E. faecium ATCC 6057 with MIC = 6.25 mg L−1. Importantly, for the most promising cocci-active benzenesulfonate derivatives the obtained MIC values were far below the cytotoxicity limit determined with respect to human normal lung fibroblasts (MRC-5). For those derivatives, the obtained IC50 values were higher than 12.3 mg L−1. The results of antimicrobial activity and cytotoxicity indicate that the tested compounds can be considered as potential antibacterial agents.

Graphical abstract: Development of structurally extended benzosiloxaboroles – synthesis and in vitro biological evaluation

Supplementary files

Article information

Article type
Paper
Submitted
27 Mai 2021
Accepted
09 Jul 2021
First published
20 Jul 2021
This article is Open Access
Creative Commons BY license

RSC Adv., 2021,11, 25104-25121

Development of structurally extended benzosiloxaboroles – synthesis and in vitro biological evaluation

P. Pacholak, J. Krajewska, P. Wińska, J. Dunikowska, U. Gogowska, J. Mierzejewska, K. Durka, K. Woźniak, A. E. Laudy and S. Luliński, RSC Adv., 2021, 11, 25104 DOI: 10.1039/D1RA04127D

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