Synthesis and evaluation of novel 4-thiazolidinone-5-nitrofuran hybrids as promising antimicrobial agents

Abstract

Abstract Searching for new effective small molecules targeting resistant strains of microorganisms is an emerging task for modern medicinal chemistry. Taking into account potential antimicrobial features of 4-thiazolidinone and 5-nitrofurane pharmacophores, two series of hybrid molecules were synthesized based on 5-nitrofuran-2-carbaldehyde, bioisosteric (E)-3-(5-nitrofuran-2-yl)acrylaldehyde, and structure-modified 4-thiazolidinone scaffolds. For all synthesized compounds, antimicrobial activity screening and cytotoxicity evaluation were performed. Novel highly active hybrid molecules with a low level of toxicity were identified, showing high broad-spectrum activity towards Gram-positive and Gram-negative bacteria, fungi, in particular Staphylococcus aureus, Klebsiella pneumoniae, Corynebacterium diphtheriae, and Aspergillus niger. A preliminary SAR analysis was performed, and key structural features that influence the manifestation of antimicrobial activity were highlighted. The obtained results will contribute to the rational design of novel agents of this pharmacological profile among 4-thiazolidinone-5-nitrofuran hybrids and related heterocyclic molecules.