Synthesis and antibacterial evaluation of novel 4-alkyl substituted phenyl β-aldehyde ketone derivatives

A series of novel 4-alkylphenyl β-aldehyde ketones and their derivatives were designed and synthesized on the basis of the chemical structures of Houttuynin and β-lactam antibiotics. Antibacterial activities of these compounds were investigated. The results demonstrated that most of the compounds tested had moderate antibacterial activities against Gram-positive pathogen Staphylococcus aureus (ATTC-25923) than Houttuynin, and Gram-positive bacteria were more susceptible to the compounds than Gram-negative bacteria. Compound 23 was found to be the most potent compound with MIC of 1.0 μg/mL against S. aureus. Particularly, compounds 16, 22 and 23 showed more active antibacterial activities against the clinically important pathogenic bacteria, methicillin-resistant S. aureus (MRSA) than Houttuynin and levofloxacin. The preliminary structure–activity relationship (SAR) analysis suggested that (1) the introduction of appropriate alkyl substituents into position 4 of phenyl ring enhanced antibacterial activities of these compounds, and isopropyl substituent might be more favorable; (2) the presence of ketone carbonyl moiety might play a vital role in determining significant antibacterial activities of these compounds.

Graphical abstract A series of novel 4-alkylphenyl β-aldehyde ketones and their derivatives were designed and synthesized in order to discover and develop novel antibacterial drugs. Compound 23 was found to be the most potent compound with minimum inhibitory concentration (MIC) of 1.0 μg/mL against Staphylococcus aureus.Figure optionsDownload full-size imageDownload as PowerPoint slide