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

Plain language summaryMetals have been used to treat microbial infections for centuries. In this context, the effects of 16 metal-based compounds against the human pathogens Scedosporium apiospermum, Scedosporium minutisporum, Scedosporium aurantiacum and Lomentospora prolificans were tested. All the 16 metal-based compounds were able to interfere with the viability of these fungal pathogens to different degrees. Among the 16 compounds, a manganese-containing compound presented the best activity against the fungal species and it presented the least toxicity to a human lung cell line. In addition, this manganese-containing compound reduced the ability of fungal cells to come together and form a type of community called biofilm. In conclusion, the manganese-containing compound presents a promising option against the multidrug-resistant filamentous fungi species belonging to the Scedosporium/Lomentospora genera. 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 mu M. Generally, Mn(II)-containing chelates were the least toxic to lung epithelial cells, particularly [Mn-2(oda)(phen)(4)(H2O)(2)][Mn-2(oda)(phen)(4)(oda)(2)].4H(2)O (MICs: 1.62-3.25 mu M: 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)(H2O)(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.

Automated summary

This study tested the effects of 16 metal-based compounds on human pathogens belonging to the Scedosporium/Lomentospora genera. All 16 compounds interfered with the viability of these fungal pathogens to different degrees. A manganese-containing compound showed the best activity against the fungal species and had the least toxicity to human lung cells. Additionally, it reduced the formation of biofilms by these fungi.