Synthesis, structure, photophysical, electrochemical properties and antibacterial activity of brominated BODIPYs as an inhibitor of DNA gyrase B of S. aureus

Abstract

BODIPYs with 3-thienyl and 4-acetamido phenyl groups substituted at the meso-position are subjected to regioselective bromination using three equivalents of [Formula: see text]-bromosuccinimide (NBS) to yield their 2-mono and 2,6-di bromoderivatives. Their photophysical, electrochemical and antimicrobial properties are investigated. This paper presents a mechanistic investigation of the antibacterial effect of brominated BODIPYs, particularly against Staphylococcus aureus. Fluorescence microscopic images reveal that the compounds are internalized effectively within the bacterial cells, making it an ideal antibacterial drug. Morphological analysis of the bacterial cells after the treatment with the test compounds showed that the compounds did not affect the cell membrane or cell wall and the antibacterial effect of these compounds is achieved via a different mechanism. The most effective compound was selected to explore the target of action. Molecular docking studies were performed on 22 selected proteins in S. aureus and the in silico results were validated by in vitro experiments. It was observed that the supercoiling activity of DNA gyrase was completely inhibited by the 2,6-dibromo-1,3,5,7-tetramethyl-8-(4-acetamido)-4-bora-3a,4a-diaza-[Formula: see text]-indacene, 3c by forming H-bonds with the ASP 81 residue of the enzyme.