Identifying a Deferiprone–Resveratrol Hybrid as an Effective Lipophilic Anti-Plasmodial Agent |
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Authors: | Supawadee Maneekesorn Hataichanok Chuljerm Pimpisid Koonyosying Chairat Uthaipibull Yongmin Ma Somdet Srichairatanakool |
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Institution: | 1.Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (S.M.); (P.K.);2.Department of Medical Technology, School of Allied Health Sciences, Walailak University, Nakornsrithammarat 80160, Thailand;3.National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani 12000, Thailand;4.School of Pharmaceutical and Chemical Engineering, Taizhou University, Taizhou 318000, China; or |
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Abstract: | Malaria i a serious health problem caused by Plasmodium spp. that can be treated by an anti-folate pyrimethamine (PYR) drug. Deferiprone (DFP) is an oral iron chelator used for the treatment of iron overload and has been recognized for its potential anti-malarial activity. Deferiprone–resveratrol hybrids (DFP-RVT) have been synthesized to present therapeutic efficacy at a level which is superior to DFP. We have focused on determining the lipophilicity, toxicity and inhibitory effects on P. falciparum growth and the iron-chelating activity of labile iron pools (LIPs) by DFP-RVT. According to our findings, DFP-RVT was more lipophilic than DFP (p < 0.05) and nontoxic to blood mononuclear cells. Potency for the inhibition of P. falciparum was PYR > DFP-RVT > DFP in the 3D7 strain (IC50 = 0.05, 16.82 and 47.67 µM, respectively) and DFP-RVT > DFP > PYR in the K1 strain (IC50 = 13.38, 42.02 and 105.61 µM, respectively). The combined treatment of DFP-RVT with PYR additionally enhanced the PYR activity in both strains. DFP-RVT dose-dependently lowered LIP levels in PRBCs and was observed to be more effective than DFP at equal concentrations. Thus, the DFP-RVT hybrid should be considered a candidate as an adjuvant anti-malarial drug through the deprivation of cellular iron. |
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Keywords: | 3-hydroxypyridin-4-one iron chelator malaria Plasmodium falciparum resveratrol |
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