The synthesis and activities of novel mononuclear or dinuclear cyclen complexes bearing azole pendants as antibacterial and antifungal agents

•A series of novel cyclen compounds appending different azoles were synthesized.•Dinuclear complexes displayed broad spectrum antimicrobial activities.•The metal ions enhanced the antimicrobial activities in varying degrees.•The in vitro safeties of these promising dinuclear compounds were confirmed.

A series of novel compounds containing 1,4,7,10-tetraazacyclododecane and azoles were synthesized and characterized by 1H NMR, MS and elemental analysis. Bioactive assay manifested that some target compounds, such as 11a, 11b and 11d, displayed good and broad spectrum antimicrobial activities with relative low MIC values against most of tested strains. These dinuclear complexes gave comparable or even better antimicrobial efficiencies than the reference drugs Fluconazole and Chloromycin. The result showed that the metal ions were the key factors to enhance the antimicrobial activities for mononuclear or dinuclear complexed in varying degrees. The interaction evaluation of compound 11b with bovine serum albumin (BSA) as an example was tested by fluorescence method. The thermodynamic parameters indicated that the hydrogen bonds and van der waals forces played the major roles in the strong association between dinuclear compound and BSA. The CCK-8 tests also confirmed the safeties of these dinuclear compounds in vitro.

Graphical abstract11a: the MIC50 of Candida albicans = 0.5 μg mL−1; 11b: the MIC50 of C. albicans = 1 μg mL−1; Fluconazole: the MIC50 of C. albicans = 0.5 μg mL−1. 11a: the MIC50 of Bacillus proteus = 0.5 μg mL−1; 11b: the MIC50 of B. proteus = 1 μg mL−1. Chloromycin: the MIC50 of B. proteus = 2 μg mL−1.Figure optionsDownload full-size imageDownload as PowerPoint slide