Emerging Anticancer Activity of Candidal Glucoseamine-6-Phosphate Synthase Inhibitors upon Nanoparticle-Mediated Delivery

Numerous glutamine analogues have been reported as irreversible inhibitors of the glucosamine-6-phosphate (GlcN-6-P) synthase in pathogenic Candida albicans in the last 3.5 decades. Among the reported inhibitors, the most effective N3-(4-methoxyfumaroyl)-l-2,3-diaminopropanoic acid (FMDP) has been e...

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Veröffentlicht in:Langmuir : the ACS journal of surfaces and colloids. - 1985. - 35(2019), 15 vom: 16. Apr., Seite 5281-5293
1. Verfasser: Kertmen, Ahmet (VerfasserIn)
Weitere Verfasser: Przysiecka, Łucja, Coy, Emerson, Popenda, Łukasz, Andruszkiewicz, Ryszard, Jurga, Stefan, Milewski, Sławomir
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2019
Zugriff auf das übergeordnete Werk:Langmuir : the ACS journal of surfaces and colloids
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Antineoplastic Agents Ferric Compounds ferric oxide 1K09F3G675 Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) EC 2.6.1.16
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500 |a ErratumIn: Langmuir. 2019 Nov 5;35(44):14397. doi: 10.1021/acs.langmuir.9b03088. - PMID 31647667 
500 |a Citation Status MEDLINE 
520 |a Numerous glutamine analogues have been reported as irreversible inhibitors of the glucosamine-6-phosphate (GlcN-6-P) synthase in pathogenic Candida albicans in the last 3.5 decades. Among the reported inhibitors, the most effective N3-(4-methoxyfumaroyl)-l-2,3-diaminopropanoic acid (FMDP) has been extensively studied in order to develop its more active analogues. Several peptide-FMDP conjugates were tested to deliver FMDP to its subcellularly located GlcN-6-P synthase target. However, the rapid development of fungal resistance to FMDP-peptides required development of different therapeutic approaches to tackle antifungal resistance. In the current state of the global antifungal resistance, subcellular delivery of FMDP via free diffusion or endocytosis has become crucial. In this study, we report on in vitro nanomedical applications of FMDP and one of its ketoacid analogues, N3- trans-4-oxo-4-phenyl-2-butenoyl-l-2,3-diaminopropanoic acid (BADP). FMDP and BADP covalently attached to polyethylene glycol-coated iron oxide/silica core-shell nanoparticles are tested against intrinsically multidrug-resistant C. albicans. Three different human cancer cell lines potentially overexpressing the GlcN-6-P synthase enzyme are tested to demonstrate the immediate inhibitory effects of nanoparticle conjugates against mammalian cells. It is shown that nanoparticle-mediated delivery transforms FMDP and BADP into strong anticancer agents by inhibiting the growth of the tested cancer cells, whereas their anti-Candidal activity is decreased. This study discusses the emerging inhibitory effect of the FMDP/BADP-nanoparticle conjugates based on their cellular internalization efficiency and biocompatibility 
650 4 |a Journal Article 
650 4 |a Research Support, Non-U.S. Gov't 
650 7 |a Antineoplastic Agents  |2 NLM 
650 7 |a Ferric Compounds  |2 NLM 
650 7 |a ferric oxide  |2 NLM 
650 7 |a 1K09F3G675  |2 NLM 
650 7 |a Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)  |2 NLM 
650 7 |a EC 2.6.1.16  |2 NLM 
700 1 |a Przysiecka, Łucja  |e verfasserin  |4 aut 
700 1 |a Coy, Emerson  |e verfasserin  |4 aut 
700 1 |a Popenda, Łukasz  |e verfasserin  |4 aut 
700 1 |a Andruszkiewicz, Ryszard  |e verfasserin  |4 aut 
700 1 |a Jurga, Stefan  |e verfasserin  |4 aut 
700 1 |a Milewski, Sławomir  |e verfasserin  |4 aut 
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