1132878-61-5Relevant articles and documents
Design, synthesis and biological evaluation of a series of iron and copper chelating deferiprone derivatives as new agents active against Candida albicans
Bortolami, Martina,Pandolfi, Fabiana,Messore, Antonella,Rocco, Daniele,Feroci, Marta,Di Santo, Roberto,De Vita, Daniela,Costi, Roberta,Cascarino, Paola,Simonetti, Giovanna,Scipione, Luigi
, (2021)
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 μg/mL and 16 μg/mL respectively) and on biofilm formation (BMIC50 of 32 μg/mL and 16 μg/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.
New deferiprone derivatives as multi-functional cholinesterase inhibitors: design, synthesis and in vitro evaluation
Alcaro, Stefano,Bagetta, Donatella,Bortolami, Martina,Carafa, Camilla,Chiarotto, Isabella,Colone, Marisa,Costi, Roberta,De Vita, Daniela,Di Santo, Roberto,Feroci, Marta,Messore, Antonella,Pandolfi, Fabiana,Scipione, Luigi,Stringaro, Annarita
, (2020/05/05)
In order to obtain multi-functional molecules for Alzheimer's disease, a series of deferiprone derivatives has been synthesized and evaluated in vitro with the hypothesis that they can restore the cholinergic tone and attenuate the dyshomeostasis of the metals mainly involved in the pathology. These compounds were designed as dual binding site AChE inhibitors: they possess an arylalkylamine moiety connected via an alkyl chain to a 3-hydroxy-4-pyridone fragment, to allow the simultaneous interaction with catalytic active site (CAS) and peripheral anionic site (PAS) of the enzyme. Deferiprone moiety and 2-aminopyridine, 2-aminopyrimidine or 2,4-diaminopyrimidine groups have been incorporated into these compounds, in order to obtain molecules potentially able to chelate bio-metals colocalized in Aβ plaques and involved in the generation of radical species. Synthesized compounds were tested by enzymatic inhibition studies towards EeAChE and eqBChE using Ellman's method. The most potent EeAChE inhibitor is compound 5a, with a Ki of 788 ± 51 nM, while the most potent eqBChE inhibitors are compounds 12 and 19, with Ki values of 182 ± 18 nM and 258 ± 25 nM respectively. Selected compounds, among the most potent cholinesterases inhibitors, were able to form complex with iron and in some cases with copper and zinc. Moreover, these compounds were characterized by low toxicity on U-87 MG Cell Line from human brain (glioblastoma astrocytoma).
Conjugation to 4-aminoquinoline improves the anti-trypanosomal activity of Deferiprone-type iron chelators
Gehrke, Sebastian S.,Pinto, Erika G.,Steverding, Dietmar,Pleban, Karin,Tempone, Andre G.,Hider, Robert C.,Wagner, Gerd K.
, p. 805 - 813 (2013/02/25)
Iron is an essential growth component in all living organisms and plays a central role in numerous biochemical processes due to its redox potential and high affinity for oxygen. The use of iron chelators has been suggested as a novel therapeutic approach
