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

作　　者：Xin-Mei Peng Kannekanti Vijaya Kumar Guri L.V. Damu Cheng-He Zhou 

机构地区：[1]Institute of Bioorganic & Medicinal Chemistry,Key Laboratory of Applied chemistry of Chongqing Municipality,School of Chemistry and Chemical Engineering,Southwest University,Chongqing 400715,China

出　　处：《Science China Chemistry》2016年第7期878-894,共17页中国科学（化学英文版）

基　　金：supported by the National Natural Science Foundation of China(21172181,21372186,81450110094, 81250110089,81350110338);the Key Program from Natural Science Foundation of Chongqing(CSTC2012jjB10026);the Specialized Research Fund for the Doctoral Program of Higher Education of China(SRFDP 20110182110007)

摘　　要：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,~1H NMR,^(13)C NMR and high-resolution mass spectra(HRMS) spectra.Some of the prepared compounds showed appropriate logP_(ow) values and effective antibacterial and antifungal activities.Noticeably,compound 14 with bis-triazolyl ethanol group exhibited low minimal inhibitory concentration(MIC)value of 8 μg/mL against MRSA,which was comparable or even superior to reference drugs Norfloxacin(MIC=8μg/mL)and Chloramphenicol(MIC=16μg/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 form14-DNA complex via both hydrogen bonds and van der Waals force,which might be the factor to exert the powerful antimicrobial activity.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, 1H NMR, 13C 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 μg/mL against MRSA, which was comparable or even superior to reference drugs Norfloxacin （MIC=8 μg/mL） and Chloramphenicol （MIC=16 μg/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.

关 键 词：COUMARIN IMIDAZOLE TRIAZOLE TETRAZOLE antibacterial ANTIFUNGAL calf thymus DNA 

分 类 号：O626[理学—有机化学]