Di Maio, A.; Olleik, H.; Courvoisier-Dezord, E.; Guillier, S.; Neulat-Ripoll, F.; Haudecoeur, R.; Bolla, J.-M.; Casanova, M.; Cavalier, J.-F.; Canaan, S.; Pique, V.; Charmasson, Y.; Baydoun, E.; Hijazi, A.; Perrier, J.; Maresca, M.; Robin, M. Design and Synthesis of Novel Amino and Acetamidoaurones with Antimicrobial Activities. Antibiotics2024, 13, 300.
Di Maio, A.; Olleik, H.; Courvoisier-Dezord, E.; Guillier, S.; Neulat-Ripoll, F.; Haudecoeur, R.; Bolla, J.-M.; Casanova, M.; Cavalier, J.-F.; Canaan, S.; Pique, V.; Charmasson, Y.; Baydoun, E.; Hijazi, A.; Perrier, J.; Maresca, M.; Robin, M. Design and Synthesis of Novel Amino and Acetamidoaurones with Antimicrobial Activities. Antibiotics 2024, 13, 300.
Di Maio, A.; Olleik, H.; Courvoisier-Dezord, E.; Guillier, S.; Neulat-Ripoll, F.; Haudecoeur, R.; Bolla, J.-M.; Casanova, M.; Cavalier, J.-F.; Canaan, S.; Pique, V.; Charmasson, Y.; Baydoun, E.; Hijazi, A.; Perrier, J.; Maresca, M.; Robin, M. Design and Synthesis of Novel Amino and Acetamidoaurones with Antimicrobial Activities. Antibiotics2024, 13, 300.
Di Maio, A.; Olleik, H.; Courvoisier-Dezord, E.; Guillier, S.; Neulat-Ripoll, F.; Haudecoeur, R.; Bolla, J.-M.; Casanova, M.; Cavalier, J.-F.; Canaan, S.; Pique, V.; Charmasson, Y.; Baydoun, E.; Hijazi, A.; Perrier, J.; Maresca, M.; Robin, M. Design and Synthesis of Novel Amino and Acetamidoaurones with Antimicrobial Activities. Antibiotics 2024, 13, 300.
Abstract
The development of new and effective antimicrobial compounds is an urgent need with 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 10, 12, 15, 16, and 20). The evaluation of their cytotoxicity on human cells and of their therapeutic index (TI) showed that compounds 10 and 20 have the highest TI. Finally, screening against a large panel of pathogens confirmed that compounds 10 and 20 possess a 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 safest 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.
Biology and Life Sciences, Biology and Biotechnology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.