Anti-Pseudomonas aeruginosa activity of 1,10-phenanthroline-based drugs against both planktonic- and biofilm-growing cells

Viganor, L., Galdino, A.C., Nunes, A.P., Santos, K., Branquinha M., Devereux, M., Kellett, A., McCann, M., Santos, A. J. 

Journal of Antimicrobial Chemotherapy71 (1): 128-134, 2016.

Objectives: The beneficial antimicrobial properties of 1,10-phenanthroline (phen)-based drugs, together with the imperative need to develop new chemotherapeutic options for prevention/treatment of infections caused by MDR Gram-negative bacteria, led us to evaluate the effects of phen, 1,10-phenanthroline-5,6-dione (phendione), [Ag(phendione)2]ClO4 and [Cu(phendione)3](ClO4)2·4H2O on planktonic- and biofilm-growing Pseudomonas aeruginosa.
Methods: Thirty-two non-duplicated Brazilian clinical isolates of P. aeruginosa with distinct genetic backgrounds were used in all experiments. The effect of test compounds on planktonic bacterial proliferation was determined as recommended by CLSI protocol. The effect on biofilm formation was evaluated by crystal violet incorporation (biomass determination) and XTT (viability assay). Mature biofilm disorganization was evidenced by staining with crystal violet.
Results: Phen-based compounds presented anti-P. aeruginosa activity, but with different potencies concerning the geometric mean MIC: [Cu(phendione)3](2+) (7.76 μM) > [Ag(phendione)2](+) (14.05 μM) > phendione (31.15 μM) > phen (579.28 μM). MICs of each compound were similar irrespective of whether the P. aeruginosa isolates were susceptible or resistant to classical antimicrobials (ceftazidime, meropenem and imipenem). The pretreatment of bacteria with phen, phendione and phendione's metal derivatives at 0.5 × MIC value inhibited biofilm formation, particularly the use of [Cu(phendione)3](2+) and [Ag(phendione)2](+), which significantly reduced both biomass (48% and 44%, respectively) and viability (78% and 77%, respectively). The compounds studied also disrupted mature biofilm in a dose-dependent manner, especially [Ag(phendione)2](+) and [Cu(phendione)3](2+) (IC50, 9.39 and 10.16 μM, respectively).
Conclusions: Coordination of phendione to Ag(+) and Cu(2+) represents a new promising group of anti-infective agents, which revealed a potent anti-P. aeruginosa action against both planktonic- and biofilm-growing cells.