Structural patterns enhancing the antibacterial activity of metallacarborane-based antibiotics

05 September 2022, Version 1

Abstract

Newly developed antibiotics are supposed to treat infections caused by drug-resistant bacteria. To increase the likelihood of overcoming resistance, antibiotic candidates should be based on structures that are unknown to bacteria. This is why boron-based antibiotics offer an interesting alternative to carbon-based drugs. This work is devoted to the development of a new group of antibiotics based on abiotic metallacarborane, cobalta bis(dicabrollide) (COSAN). We managed to identify the two most promising structural patterns that cause COSAN-based compounds to be selectively active toward S. aureus: the introduction of α-amino acid amide in the organic part of the molecule and the addition of iodine directly to the metallacarborane cage. The first modification provided selective activity of the tested compounds toward S. aureus over mammalian cells through proper hydrophobic-hydrophilic balance. The second modification increased all observed biological activities. The patterns proposed in this paper can be used in the development of metallacarborane-based antibiotics that have potent antibacterial properties and low cytotoxicity.

Keywords

metallacarboranes
boron clusters
COSAN
Staphylococcus aureus
antibiotics
antibacterial activity

Supplementary materials

Title
Description
Actions
Title
Supporting Information
Description
1H NMR, 13C{1H} NMR, 11B{1H} NMR, HRMS, HPLC traces, and additional in vitro data.
Actions

Comments

Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.