Synthesis, Characterization, and Biological Evaluation of Novel N-{4-[(4-Bromophenyl)sulfonyl]benzoyl}-L-valine Derivatives

Abstract

In this article, we present the design and synthesis of novel compounds, containing in their molecules an L-valine residue and a 4-[(4-bromophenyl)sulfonyl]phenyl moiety, which belong to N-acyl-α-amino acids, 4H-1,3-oxazol-5-ones, 2-acylamino ketones, and 1,3-oxazoles chemotypes. The synthesized compounds were characterized through elemental analysis, MS, NMR, UV/VIS, and FTIR spectroscopic techniques, the data obtained being in accordance with the assigned structures. Their purities were verified by reversed-phase HPLC. The new compounds were tested for antimicrobial action against bacterial and fungal strains, for antioxidant activity by DPPH, ABTS, and ferric reducing power assays, and for toxicity on freshwater cladoceran Daphnia magna Straus. Furthermore, in silico studies were performed concerning the potential antimicrobial effect and toxicity. The results of antimicrobial activity, antioxidant effect, and toxicity assays, as well as of in silico analysis revealed a promising potential of N-{4-[(4-bromophenyl)sulfonyl]benzoyl}-L-valine and 2-{4-[(4-bromophenyl)sulfonyl]phenyl}-4-isopropyl-4H-1,3-oxazol-5-one for developing novel antimicrobial agents to fight Gram-positive pathogens, and particularly Enterococcus faecium biofilm-associated infections.