Effect of a novel iron chelator, 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one, and green tea extract on plasmodium spp. growth inhibition

ผลของยาขับเหล็กตัวใหม่ 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one และสารสกัดชาเขียวที่ยับยั้งการเจริญเติบโตของเชื้อพลาสโมเดียม

Name: Phitsinee Thipubon

ThaSH: Plasmodium falciparum

Classification :.DDC: 572

ThaSH: Clinical biochemistry

Abstract: Iron is an essential trace element required by all living organisms including malaria parasites (Plasmodium spp.) for many biochemical reactions. Malaria parasites can take up the iron from outside and/or inside parasitized red blood cells (PRBC). Iron chelators such as desferrioxamine (DFO), deferiprone (DFP) and deferasirox (DFX) are widely used for treatment of thalassemia-related iron overload and inhibit parasite growth at levels which are non-toxic to mammalian cells. Our novel synthetic iron chelator, 1-(N-acetyl-6-aminohexyl)-3-hydroxypyridin-4-one (CM1), is a bidentate chelator which is more lipophilic than DFP. CM1 effectively chelates plasma non-transferrinbound serum iron (NTBI), labile plasma iron (LPI) and intracellular labile iron pools (LIP). Importantly, the compound is not toxic to normal cell cultures up to 48 hours and mice up to 8 months. Green tea (Camellia sinensis) extract (GTE) is abundant in epigallocatechin 3-gallate (EGCG) which exhibits strong antioxidant and iron-chelating activities. In this study, we examined inhibitory effect of CM1 and GTE on growth of P. falciparum in vitro and P. berghei in mice. Fluorescent probes-associated flow cytometric technique was used to determine %parasitemia, LIP and reactive oxygen species (ROS) in the PRBC. We found the inhibitory concentration at 50% against P. falciparum (IC50) of DFO, GTE, CM1, DFX and DFP were 14.09, 21.11, 35.14, 44.71 and 58.25 µM, respectively. Importantly, CM1 was more effective in decreasing LIP level in the P. falciparum-infected RBC than DFP (p <0.05). GTE could reduce intracellular ROS level except CM1 and DFP treatment. In 4-days suppressive test, CM1 inhibited growth of P. berghei in mice at effective dose at 50% (ED50) value of 56.91 mg/kg. In combination treatments, in vitro anti-malarial activity of PYR was antagonized by CM1 and GTE at low concentrations, and was synergized by the compounds at high concentrations. Obviously, only GTE synergized PYR activity in P. berghei-infected mice. Possibly, CM1 and GTE could interfere with the uptake of exogenous iron into or deplete intracellular labile iron in malaria parasites, leading to inhibition of their growth. CM1 and GTE would be adjunctive with pyrimethamine to enhance its anti-malarial activity and minimize drug resistance

Chiang Mai University Library

Address: CHIANG MAI

Email: cmulibref@cmu.ac.th

Name: Voravuth Soms

Role: Chairman

Name: Somdet Srichairatanakool

Role: Member

Name: Chairat UthaiPibull

Role: Member

Name: Wachiraporn Tipsuwan

Role: Member

Name: Jetsada RuangsuriYa

Role: Member

Created: 2014

Modified: 2017-09-21

Issued: 2017-09-21

วิทยานิพนธ์/Thesis

application/pdf

CallNumber: Th 572 P573E

eng

DegreeName: Master of Science

Level: ปริญญาโท

Descipline: Biochemistry

Grantor: มหาวิทยาลัยเชียงใหม่

ลำดับที่.	ชื่อแฟ้มข้อมูล	ขนาดแฟ้มข้อมูล	จำนวนเข้าถึง	วัน-เวลาเข้าถึงล่าสุด
1	bioch61214ptu_full.pdf	2.72 MB	1	2022-08-11 17:43:01

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