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

Abstract

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.

Keywords: Anti-biofilm; Green synthesis; Isoxazole-sulfonamide; Isoxazoline-sulfonamide; Pseudomonas aeruginosa.