4’-hydroxychalcones antibacterial activity: a combination between membrane and divisional septum disruptions

Natural chalcones have shown antibacterial activity1. Few studies about synthetic hydroxychalcones have been described2. Our investigation aimed to evaluate hydroxychalcones antibacterial activity against Gram-positive and Gram-negative species, as well as their targets. Antibacterial activity was determined by Resazurin Microtiter Assay (REMA) and 4’-hydroxychalcone (4) demonstrated activity against Staphylococcus aureus and Pseudomonas aeruginosa. Experiments with Bacillus subtilis mutant strain expressing FtsZ (Filamentous temperature-sensitive protein Z) labelled by GFP (green fluorescent protein) (amy:pspac-ftsZ-gfpmut1) indicated 4 was able to perturb divisional septum dynamics at 15 and 30 min. Biochemical assays with FtsZ demonstrated 4 did not inhibit its GTPase activity and further studies to explore other divisome proteins as target are ongoing. Fluorescence microscopy tests with B. subtilis 168 using SYTO 9 and propidium iodide fluorophores indicated 4 disrupt bacterial membrane at 30 min. In addition, 4 exhibited low toxicity against spontaneously transformed immortal human keratinocyte cells (HaCaT line).