Active Cu(II), Mn(II) and Ag(I) 1,10-phenanthroline/1,10-phenanthroline-5,6-dione/dicarboxylate chelates: effects on Scedosporium .

Background: Scedosporium/Lomentospora species are human pathogens resistant to almost all antifungals currently available in clinical practice. Methods: The effects of 16 1,10-phenanthroline (phen)/1,10-phenanthroline-5,6-dione/dicarboxylate chelates containing Cu(II), Mn(II) and Ag(I) against Scedosporium apiospermum , Scedosporium minutisporum , Scedosporium aurantiacum and Lomentospora prolificans were evaluated. Results: To different degrees, all of the test chelates inhibited the viability of planktonic conidial cells, displaying MICs ranging from 0.029 to 72.08 μM. Generally, Mn(II)-containing chelates were the least toxic to lung epithelial cells, particularly [Mn 2 (oda)(phen) 4 (H 2 O) 2 ][Mn 2 (oda)(phen) 4 (oda) 2 ].4H 2 O (MICs: 1.62-3.25 μM: selectivity indexes >64). Moreover, this manganese-based chelate reduced the biofilm biomass formation and diminished the mature biofilm viability. Conclusion: [Mn 2 (oda)(phen) 4 (H 2 O) 2 ][Mn 2 (oda)(phen) 4 (oda) 2 ].4H 2 O opens a new chemotherapeutic avenue for the deactivation of these emergent, multidrug-resistant filamentous fungi.