Design and Synthesis of Novel Amino and Acetamidoaurones with Antimicrobial Activities

The development of new and effective antimicrobial compounds is urgent due to the emergence of resistant bacteria. Natural plant flavonoids are known to be effective molecules, but their activity and selectivity have to be increased. Based on previous aurone potency, we designed new aurone derivativ...

Full description

Saved in:
Bibliographic Details
Published in:Antibiotics (Basel) 2024-04, Vol.13 (4), p.300
Main Authors: Di Maio, Attilio, Olleik, Hamza, Courvoisier-Dezord, Elise, Guillier, Sophie, Neulat-Ripoll, Fabienne, Haudecoeur, Romain, Bolla, Jean-Michel, Casanova, Magali, Cavalier, Jean-François, Canaan, Stéphane, Pique, Valérie, Charmasson, Yolande, Baydoun, Elias, Hijazi, Akram, Perrier, Josette, Maresca, Marc, Robin, Maxime
Format: Article
Language:English
Subjects:
Amino groups
anti-bacterial agents
Antimicrobial activity
Antimicrobial agents
aurone
Bacteria
Bacteriology
Bioflavonoids
Cells
Chemical Sciences
Cytotoxicity
cytotoxicity tests
E coli
Flavones
Flavonoids
Fungi
Gram-negative bacteria
Gram-positive bacteria
Life Sciences
Methicillin
Microbiology and Parasitology
Organic chemistry
Pathogens
Staphylococcus infections
structure-activity relationship
Tuberculosis
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The development of new and effective antimicrobial compounds is urgent due to the emergence of resistant bacteria. Natural plant flavonoids are known to be effective molecules, but their activity and selectivity have to be increased. Based on previous aurone potency, we designed new aurone derivatives bearing acetamido and amino groups at the position 5 of the A ring and managing various monosubstitutions at the B ring. A series of 31 new aurone derivatives were first evaluated for their antimicrobial activity with five derivatives being the most active (compounds , , , , and ). The evaluation of their cytotoxicity on human cells and of their therapeutic index (TI) showed that compounds and had the highest TI. Finally, screening against a large panel of pathogens confirmed that compounds and possess large spectrum antimicrobial activity, including on bioweapon BSL3 strains, with MIC values as low as 0.78 µM. These results demonstrate that 5-acetamidoaurones are far more active and safer compared with 5-aminoaurones, and that benzyloxy and isopropyl substitutions at the B ring are the most promising strategy in the exploration of new antimicrobial aurones.
ISSN:2079-6382
2079-6382
DOI:10.3390/antibiotics13040300