Green synthesis and anti-biofilm activities of 3,5-disubstituted isoxazoline/isoxazole-linked secondary sulfonamide derivatives on Pseudomonas aeruginosa

• Published in: Bioorganic & medicinal chemistry letters 2023-11, Vol.96, p.129517-129517, Article 129517
• Main Authors: El Mahmoudi, Ayoub, Tareau, Anne-Sophie, Barreau, Magalie, Chevalier, Sylvie, Hourma, Chaimae, Demange, Luc, Benhida, Rachid, Bougrin, Khalid
• Format: Article
• Language: English
• Subjects: Anti-biofilm; Chemical Sciences; Green synthesis; Isoxazole-sulfonamide; Isoxazoline-sulfonamide; Pseudomonas aeruginosa
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2023.129517

[Display omitted] •Green Synthesis one-pot three-step cascade of novel isoxazoline/isoxazole-linked sulfonamides.•Regioselective synthesis ofisoxazoline/isoxazole-linked secondary sulfonamides, using MgI2/K2CO3/Oxonein water.•The new compounds were tested for their anti-biofilm activities against Pseudomonas aeruginosa.•Compounds 5a and 6a displayed potent broad-spectrum anti-biofilm activity. The search for new classes of antibiotics is a real concern of public health due to the emergence of multi-resistant bacteria strains. We report herein the synthesis and characterization of a new series of 13 molecules combining isoxazoline/isoxazole sulfonamides and hydrazides motives. These molecules were obtained according to a costless eco-friendly procedure, and a one-pot three-step cascade synthesis under ultrasonic cavitation. All the synthesized compounds were fully characterized by HRMS, 1H NMR, 13C NMR spectroscopy and HPLC analysis. These new molecules have been evaluated against the major human opportunistic pathogen Pseudomonas aeruginosa to determine their potential to affect its growth and biofilm formation or dispersion. Two derivatives (5a and 6a) demonstrated their ability to destabilize a mature biofilm by about 50 % within 24 h. This may pave the way to the development of a new class of compounds affecting biofilm, which are easy to synthesize according to green chemistry processes.