N-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl)thiosemicarbazones of 6-alkoxy-2-oxo-2H-chromene-4-carbaldehydes: synthesis, evaluation of their antibacterial, anti-MRSA, antifungal activity, and docking study

Abstract

Reaction of 6-alkoxy-2-oxo-2H-chromen-4-carbaldehydes with N-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl)thiosemicarbazide yielded corresponding thiosemicarbazones having 2H-chromen-2-one ring. In vitro evaluations showed that these 2H-chromen-2-one compounds exhibited remarkable antibacterial and antifungal activities against some typical bacteria and fungi. Representative compounds with MIC values of 0.78 − 1.56 μg/mL were 6c, 6g (against S. aureus), 6a, 6f (against S. epidermidis) (Gram-positive bacterial strains), 6e, 6g (against E. coli), 6b, 6e (against K. pneumoniae), and 6d–f (against S. typhimurium) (Gram-negative bacterial strains). Almost all thiosemicarbazones 6a–g had no activity against Gram-positive bacterial strain B. subtilis at these MIC values. Some compounds had strong inhibitory activity against several bacteria, such as 6b (for K. pneumoniae and S. typhimurium), 6d, 6e (for E. coli, K. pneumoniae, and S. typhimurium), 6f (for S. aureus, E. coli, and S. typhimurium), and 6g (for B. subtilis, S. aureus, E. coli, and K. pneumoniae). Some compounds had remarkable inhibitory activity against three clinical MRSA isolates with MIC values of 0.78–6.25 μg/mL. Docking study showed that compound 6g is compatible with the active site of S. aureus DNA gyrase 2XCT, which suggested that the tested compounds inhibited the synthesis of this enzyme.