Halogenated 3-Nitro-2<i>H</i>-Chromenes as Potential Agents Against Multidrug-Resistant Bacteria

Abstract

Introduction/Objectives: Nosocomial infections caused by S. aureus and S. epidermidis resistant strains are an important cause of morbidity and mortality worldwide. Due to the increasing rate of resistance to conventional antibiotics, the discovery of new antibiotic drugs is crucial to keep pace with the evolution of these pathogenic bacterial species. Methods: The 3-nitro-2H-chromene moiety is present in several compounds with potent antibacterial activity; based on these previous studies, we report herein the synthesis of 20 new 2-aryl-3-nitro-2H-chromene derivatives and the evaluation of their antibacterial potential in vitro. Results: Mono-halogenated nitrochromenes showed moderate anti-staphylococcal activity with MIC values of 8–32 μg/mL, whereas tri-halogenated 3-nitro-2H-chromenes displayed potent anti-staphylococcal activities with MIC values of 1–8 μg/mL. Notably, 2-(4-bromophenyl)-6-bromo-8-chloro-3-nitro-2H-chromene 5s was the best antibacterial agent in the series against multidrug-resistant strains of S. aureus and S. epidermidis with MIC values of 4 μg/mL and 1–4 μg/mL, respectively. Conclusions: nitrochromene 5s shows a good safety profile, so it can be considered as a lead for further development.

Keywords

• chromenes
• nitro derivatives
• antibacterial
• MDR bacteria
• halogenated drugs