Add time:09/07/2019         Source:sciencedirect.com

Copper(II) complexes of the general structure [Cu(L1)(L2)]2 + where L1 is (1S,2S)-diaminocyclohexane or (1R,2R)-diaminocyclohexane and L2 is 3,4,7,8-tetramethyl-1,10-phenanthroline (TMP) or 4,7-diphenyl-1,10-phenanthroline (DIP), have been investigated for their in vitro antimicrobial spectrum of activity, short-term antimicrobial efficacy, and DNA-binding affinity. Minimal inhibitory concentrations (MIC) against an expanded bacterial and fungal panel, confirmed that these mixed-ligand complexes are primarily effective against Gram-positive bacteria (MIC 4–8 µg/mL, 5.6–13.1 µM), with DIP coordinated complexes more effective than TMP counterparts. In contrast, TMP coordinated complexes demonstrated superior anti-Candida activity (MIC 8–16 µg/mL, 13.1–26.1 µM) than DIP variants, as well as 5-fluorocytosine. Growth inhibition by mixed-ligand complexes against Staphylococcus aureus and Enterococcus faecalis was evident within 0.5 h of exposure, in comparison to ampicillin. Similarly, these complexes but not ampicillin demonstrated bactericidal activity in non-proliferating conditions. All complexes exhibited DNA binding affinities within a similar magnitude of ethidium bromide (Ka ~ 105 M− 1), as derived from linear dichroism binding studies and fluorescent probe displacement assays with ethidium bromide or Hoechst 33258. Results imply that these copper(II) complexes have different modes of action to established antibiotics, ampicillin and 5-fluorocytosine, and provide further insight into development of effective antimicrobial agents.

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