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2-tert-butyl-primaquine exhibit potent blood schizontocidal antimalarial activity via inhibition of heme crystallization
Malaria Journal volume 9, Article number: P69 (2010)
Primaquine (PQ) is the only 8-quinolinamine available to treat the malarial parasites in the infections caused by Plasmodium vivax and P. ovale. PQ has broad range of antimalarial activities, including efficacy as a causal prophylactic, gametocytocide, and sporontocide. These encouraging pharmacological properties make PQ an ideal drug to emulate while designing new antimalarials with improved activities (). The placement of a metabolically stable tert-butyl group at the C-2 position of a quinoline ring in PQ (2-tert-Butyl-Primaquine - BPQ) results in a tremendous improvement in blood schizontocidal antimalarial activity ([1, 2]). Because free heme released from hemoglobin catabolism in a malarial parasite is highly toxic, the parasite protects itself mainly by crystallization of heme into insoluble nontoxic hemozoin (). In this study, we investigate the mechanism of blood schizontocidal activity of BPQ.
The results described herein indicate that a major improvement in the blood-schizontocidal antimalarial activity of 2-tert-butylprimaquine might be due to a disturbance of heme catabolism pathway in the malarial parasite.
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Jain M, Vangapandu S, Sachdeva S, Jain R: Synthesis and blood-schizontocidal antimalarial activities of 2-substituted/2,5-disubstituted-8-quinolinamines and some of their amino acid conjugates. Bioorg Med Chem. 2004, 12: 1003-1010. 10.1016/j.bmc.2003.12.029.
Egan TJ, Combrinck JM, Egan J, Hearne GR, Marques HM, Ntenteni S, Sewell BT, Smith PJ, Taylor D, van Schalkwyk DA, Walden JC: Fate of haem iron in the malaria parasite Plasmodium falciparum. Biochem J. 2002, 365: 343-347. 10.1042/BJ20020793.
Our sincere thanks to all members in Structural Biotechnology Laboratory, Department of Applied Biology, Kyoto Institute of Technology who have contributed to and worked on this study.
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Thanh Thuy, N.N., Tien, H.N., Jain, R. et al. 2-tert-butyl-primaquine exhibit potent blood schizontocidal antimalarial activity via inhibition of heme crystallization. Malar J 9, P69 (2010) doi:10.1186/1475-2875-9-S2-P69
- Infectious Disease
- Pharmacological Property
- Major Improvement