Effects of Synthetic Siderophores on Proliferation of<i>Plasmodium falciparum</i>in Infected Human Erythrocytes

Rotheneder, Andrea; Fritsche, Gernot; Heinisch, Lothar; Möllmann, Ute; Heggemann, Susanne; Larcher, Clara; Weiss, Günter

doi:10.1128/aac.46.6.2010-2013.2002

Cited by 11 publications

(9 citation statements)

References 18 publications

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“…The activity of 6 may result from the strong chelation of DFO-E 6 with iron from the culture medium of P. falciparum, causing iron deficit and finally cell death [32]. This observation was consistent with the reported antiplasmodial activities of siderophores in literature [33][34][35][36].…”

Section: Biological Testsupporting

confidence: 88%

Signalling and Bioactive Metabolites from Streptomyces sp. RK44

Fang

Maglangit

et al. 2020

Molecules

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Streptomyces remains one of the prolific sources of structural diversity, and a reservoir to mine for novel natural products. Continued screening for new Streptomyces strains in our laboratory led to the isolation of Streptomyces sp. RK44 from the underexplored areas of Kintampo waterfalls, Ghana, Africa. Preliminary screening of the metabolites from this strain resulted in the characterization of a new 2-alkyl-4-hydroxymethylfuran carboxamide (AHFA) 1 together with five known compounds, cyclo-(L-Pro-Gly) 2, cyclo-(L-Pro-L-Phe) 3, cyclo-(L-Pro-L-Val) 4, cyclo-(L-Leu-Hyp) 5, and deferoxamine E 6. AHFA 1, a methylenomycin (MMF) homolog, exhibited anti-proliferative activity (EC50 = 89.6 µM) against melanoma A2058 cell lines. This activity, albeit weak is the first report amongst MMFs. Furthermore, the putative biosynthetic gene cluster (ahfa) was identified for the biosynthesis of AHFA 1. DFO-E 6 displayed potent anti-plasmodial activity (IC50 = 1.08 µM) against P. falciparum 3D7. High-resolution electrospray ionization mass spectrometry (HR ESIMS) and molecular network assisted the targeted-isolation process, and tentatively identified six AHFA analogues, 7–12 and six siderophores 13–18.

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Section: Biological Testsupporting

confidence: 88%

Signalling and Bioactive Metabolites from Streptomyces sp. RK44

Fang

Maglangit

et al. 2020

Molecules

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“…Perhaps for these reasons, desferrioxamine did not reduce mortality in clinical trials (Thuma et al , 1998a), despite some early promise (Gordeuk et al , 1992b), nor did the orally active iron chelator deferiprone (Thuma et al , 1998b). Nevertheless, the particular sensitivity of Plasmodium blood‐stage growth to iron chelators, noted by Glickstein and colleagues among others (Glickstein et al , 1996), means that the iron chelation approach might be beneficial, and further iron‐binding molecules aimed at halting Plasmodium growth are being developed (Pradines et al , 2006; Rotheneder et al , 2002). One additional factor to bear in mind, however, is that the potent antimalarial artemisinin requires iron for its action—so that co‐administration with iron chelators is probably ill‐advised (Meshnick et al , 1993; Weinberg & Moon, 2009).…”

Section: The Importance Of Iron For Plasmodium Developmentmentioning

confidence: 99%

Superinfection in malaria: Plasmodium shows its iron will

2011

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EMBO reports VOL 12 | NO 12 | 2011 1233 review review After the bite of a malaria-infected mosquito, the Plasmodium sporozoite infects liver cells and produces thousands of merozoites, which then infect red blood cells, causing malaria. In malaria-endemic areas, several hundred infected mosquitoes can bite an individual each year, increasing the risk of superinfection. However, in infants that are yet to acquire immunity, superinfections are infrequent. We have recently shown that blood-stage parasitaemia, above a minimum threshold, impairs the growth of a subsequent sporozoite infection of liver cells. Blood-stage parasites stimulate the production of the host iron-regulatory factor hepcidin, which redistributes iron away from hepatocytes, reducing the development of the iron-dependent liver stage. This could explain why Plasmodium superinfection is not often found in young nonimmune children. Here, we discuss the impact that such protection from superinfection might have in epidemiological settings or in programmes for controlling malaria, as well as how the induction of hepcidin and redistribution of iron might influence anaemia and the outcome of non-Plasmodium co-infections.

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“…In fact, they are used for their antibacterial activity against antibiotic-resistant bacteria (Flanagan et al, 2011), for iron nutrition in several organisms (Sharma & Johri, 2003;Siebner-Freibach, Hadar, & Chen, 2003) and for alleviation of iron overload in medicine (Lindsey & Olin, 2007). Furthermore, iron deprivation is an appropriate strategy for therapy of breast cancer (Pahl, Horwitz, Horwitz, & Horwitz, 2001), malaria (Rotheneder et al, 2002) and microbial infection through immunomodulatory action or the synthesis of siderophore-antibiotic conjugates (i.e. pyoverdin/β-lactams) (Budzikiewicz, 2001).…”

Section: Marine Bacterial Secondary Metabolites: Structure and Functionmentioning

confidence: 97%