Coumarin-derived azolyl ethanols: synthesis, antimicrobial evaluation and preliminary action mechanism

A series of coumarin-derived azolyl ethanols including imidazolyl, triazolyl, tetrazolyl, benzotriazolyl, thiol-imidazolyl and thiol-triazolyl ones were conveniently synthesized and characterized by IR, H-1 NMR, C-13 NMR and high-resolution mass spectra (HRMS) spectra. Some of the prepared compounds showed appropriate logPow values and effective antibacterial and antifungal activities. Noticeably, compound 14 with bis-triazolyl ethanol group exhibited low minimal inhibitory concentration (MIC) value of 8 mg/mL against MRSA, which was comparable or even superior to reference drugs Norfloxacin (MIC=8 mg/mL) and Chloramphenicol (MIC=16 mg/mL). It could also effectively inhibit the growth of the tested fungal strains compared to Fluconazole. Further binding studies of coumarin 14 with calf thymus DNA were investigated by UV-Vis absorption and fluorescence spectroscopy. It was found that compound 14 could interact with calf thymus DNA by groove binding to form 14-DNA complex via both hydrogen bonds and van der Waals force, which might be the factor to exert the powerful antimicrobial activity.