Candida albicans, in specific conditions, is responsible of severe invasive systemic candidiasis that are related to its ability to produce biofilm on biological and artificial surfaces. Many studies reported the role of iron in fungal growth and virulence and the ability of metal chelating agents to interfere with C. albicans metabolism, virulence and biofilm formation. Here we report the activity of 3-hydroxy-1,2-dimethyl-4(1H)-pyridinone (deferiprone) derivatives against C. albicans planktonic cells and biofilm. Some of the studied compounds (2b and 3b) were able to chelate Fe(III) and Cu(II), and showed an interesting activity on planktonic cells (MIC50 of 32 mu g/mL and 16 mu g/mL respectively) and on biofilm formation (BMIC50 of 32 mu g/mL and 16 mu g/mL respectively) in cultured ATCC 10,231C. albicans; this activity was reduced, in a concentration dependent way, by the addition of Fe(III) and Cu (II) to the culture media. Furthermore, the most active compound 3b showed a low toxicity on Galleria mellonella larvae.
Bortolami, M., Pandolfi, F., Messore, A., Rocco, D., Feroci, M., Di Santo, R., et al. (2021). Design, synthesis and biological evaluation of a series of iron and copper chelating deferiprone derivatives as new agents active against Candida albicans. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 42 [10.1016/j.bmcl.2021.128087].
Design, synthesis and biological evaluation of a series of iron and copper chelating deferiprone derivatives as new agents active against Candida albicans
Rocco, Daniele;
2021-01-01
Abstract
Candida albicans, in specific conditions, is responsible of severe invasive systemic candidiasis that are related to its ability to produce biofilm on biological and artificial surfaces. Many studies reported the role of iron in fungal growth and virulence and the ability of metal chelating agents to interfere with C. albicans metabolism, virulence and biofilm formation. Here we report the activity of 3-hydroxy-1,2-dimethyl-4(1H)-pyridinone (deferiprone) derivatives against C. albicans planktonic cells and biofilm. Some of the studied compounds (2b and 3b) were able to chelate Fe(III) and Cu(II), and showed an interesting activity on planktonic cells (MIC50 of 32 mu g/mL and 16 mu g/mL respectively) and on biofilm formation (BMIC50 of 32 mu g/mL and 16 mu g/mL respectively) in cultured ATCC 10,231C. albicans; this activity was reduced, in a concentration dependent way, by the addition of Fe(III) and Cu (II) to the culture media. Furthermore, the most active compound 3b showed a low toxicity on Galleria mellonella larvae.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
