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Inhibitory effect of novel iron chelator, 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) and green tea extract on growth of Plasmodium falciparum.

Thipubon P, Uthaipibull C, Kamchonwongpaisan S, Tipsuwan W, Srichairatanakool S - Malar. J. (2015)

Bottom Line: The IC50 values of DFO, GTE, CM1, DFX and DFP against P. falciparum were 14.09, 21.11, 35.14, 44.71 and 58.25 µM, respectively.Importantly, CM1 was more effective in reducing LIP levels in the P. falciparum culture than DFP (p < 0.05).CM1 and GTE exhibit anti-malarial activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Faculty of Medicine, Chiang Mai University, 110 Inthawaroros Street, Tambol Sriphum, Amphur Muang, Chiang Mai, 50200, Thailand. pedassy@hotmail.com.

ABSTRACT

Background: Iron is an essential micronutrient required by all living organisms including malaria parasites (Plasmodium spp.) for many biochemical reactions, especially growth and multiplication processes. Therefore, malaria parasite needs to take up the iron from outside or/and inside the parasitized red blood cells (PRBC). Iron chelators are widely used for the treatment of thalassaemia-related iron overload and also inhibit parasite growth at levels that are non-toxic to mammalian cells.

Methods: Inhibitory effect of 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) and green tea extract (GTE) on the growth of malaria parasite Plasmodium falciparum was compared with standard chelators including desferrioxamine (DFO), deferiprone (DFP) and deferasirox (DFX). A flow cytometric technique was used to enumerate PRBC stained with SYBR Green I fluorescent dye. The labile iron pool (LIP) was assayed using the calcein-acetoxymethyl fluorescent method.

Results: The IC50 values of DFO, GTE, CM1, DFX and DFP against P. falciparum were 14.09, 21.11, 35.14, 44.71 and 58.25 µM, respectively. Importantly, CM1 was more effective in reducing LIP levels in the P. falciparum culture than DFP (p < 0.05).

Conclusions: CM1 and GTE exhibit anti-malarial activity. They could interfere with uptake of exogenous iron or deplete the intracellular labile iron pool in malaria parasites, leading to inhibition of their growth.

No MeSH data available.


Related in: MedlinePlus

Sensitivity of P. falciparum to anti-malarial drugs, iron chelators and tested compounds. Data are obtained from three independent triplicate experiments and expressed as mean ± SD. Their IC50 values are shown in dotted lines
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Fig1: Sensitivity of P. falciparum to anti-malarial drugs, iron chelators and tested compounds. Data are obtained from three independent triplicate experiments and expressed as mean ± SD. Their IC50 values are shown in dotted lines

Mentions: As shown in Fig. 1, DFO, GTE, CM1, DFX and DFP had different efficiencies in inhibition of P. falciparum growth and development as shown as % parasitaemia. Their IC50 values are 10.09, 21.11, 35.14, 44.71 and 58.25 μM, respectively. In comparison, DHA and PYR (IC50 = 1.930 and 37.89 nM, respectively) were much more potent than these compounds. In combined treatment with 30 nM PYR, CM1 (50–200 μM) significantly enhanced the anti-malarial activity of the PYR per se (mean difference of parasite growth = 24.4, 24.4 and 24.6 %, respectively). Incredibly, GTE (50–200 μM EGCG equivalent) significantly enhanced the PYR activity min a concentration-dependent manner (mean differences of parasite growth = 44.2, 44.9 and 47.7 %, respectively) (Fig. 2). Remarkably, the PYR-GTE synergy seemed to be greater than the PYR-CM1.Fig. 1


Inhibitory effect of novel iron chelator, 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) and green tea extract on growth of Plasmodium falciparum.

Thipubon P, Uthaipibull C, Kamchonwongpaisan S, Tipsuwan W, Srichairatanakool S - Malar. J. (2015)

Sensitivity of P. falciparum to anti-malarial drugs, iron chelators and tested compounds. Data are obtained from three independent triplicate experiments and expressed as mean ± SD. Their IC50 values are shown in dotted lines
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4590262&req=5

Fig1: Sensitivity of P. falciparum to anti-malarial drugs, iron chelators and tested compounds. Data are obtained from three independent triplicate experiments and expressed as mean ± SD. Their IC50 values are shown in dotted lines
Mentions: As shown in Fig. 1, DFO, GTE, CM1, DFX and DFP had different efficiencies in inhibition of P. falciparum growth and development as shown as % parasitaemia. Their IC50 values are 10.09, 21.11, 35.14, 44.71 and 58.25 μM, respectively. In comparison, DHA and PYR (IC50 = 1.930 and 37.89 nM, respectively) were much more potent than these compounds. In combined treatment with 30 nM PYR, CM1 (50–200 μM) significantly enhanced the anti-malarial activity of the PYR per se (mean difference of parasite growth = 24.4, 24.4 and 24.6 %, respectively). Incredibly, GTE (50–200 μM EGCG equivalent) significantly enhanced the PYR activity min a concentration-dependent manner (mean differences of parasite growth = 44.2, 44.9 and 47.7 %, respectively) (Fig. 2). Remarkably, the PYR-GTE synergy seemed to be greater than the PYR-CM1.Fig. 1

Bottom Line: The IC50 values of DFO, GTE, CM1, DFX and DFP against P. falciparum were 14.09, 21.11, 35.14, 44.71 and 58.25 µM, respectively.Importantly, CM1 was more effective in reducing LIP levels in the P. falciparum culture than DFP (p < 0.05).CM1 and GTE exhibit anti-malarial activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Faculty of Medicine, Chiang Mai University, 110 Inthawaroros Street, Tambol Sriphum, Amphur Muang, Chiang Mai, 50200, Thailand. pedassy@hotmail.com.

ABSTRACT

Background: Iron is an essential micronutrient required by all living organisms including malaria parasites (Plasmodium spp.) for many biochemical reactions, especially growth and multiplication processes. Therefore, malaria parasite needs to take up the iron from outside or/and inside the parasitized red blood cells (PRBC). Iron chelators are widely used for the treatment of thalassaemia-related iron overload and also inhibit parasite growth at levels that are non-toxic to mammalian cells.

Methods: Inhibitory effect of 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) and green tea extract (GTE) on the growth of malaria parasite Plasmodium falciparum was compared with standard chelators including desferrioxamine (DFO), deferiprone (DFP) and deferasirox (DFX). A flow cytometric technique was used to enumerate PRBC stained with SYBR Green I fluorescent dye. The labile iron pool (LIP) was assayed using the calcein-acetoxymethyl fluorescent method.

Results: The IC50 values of DFO, GTE, CM1, DFX and DFP against P. falciparum were 14.09, 21.11, 35.14, 44.71 and 58.25 µM, respectively. Importantly, CM1 was more effective in reducing LIP levels in the P. falciparum culture than DFP (p < 0.05).

Conclusions: CM1 and GTE exhibit anti-malarial activity. They could interfere with uptake of exogenous iron or deplete the intracellular labile iron pool in malaria parasites, leading to inhibition of their growth.

No MeSH data available.


Related in: MedlinePlus