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• W2924118092 abstract "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." @default.
• W2924118092 created "2019-04-01" @default.
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• W2924118092 date "2019-03-26" @default.
• W2924118092 modified "2023-10-12" @default.
• W2924118092 title "Emerging Anticancer Activity of Candidal Glucoseamine-6-Phosphate Synthase Inhibitors upon Nanoparticle-Mediated Delivery" @default.
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• W2924118092 doi "https://doi.org/10.1021/acs.langmuir.8b04250" @default.
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• W2924118092 hasPublicationYear "2019" @default.
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