Hemozoin Biocrystallization in Plasmodium falciparum and the antimalarial activity of crystallization inhibitors

School of Biochemistry, Genetics, Microbiology and Plant Pathology, University of KwaZulu-Natal, P.O. Box XO1, Scottsville, 3209, Pietermaritzburg, South Africa.
Parasitology Research (Impact Factor: 2.1). 04/2007; 100(4):671-6. DOI: 10.1007/s00436-006-0313-x
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    • "This process occurs in an acidic organelle vacuole. Chloroquine, as a weak base, is accumulated in a vacuole and prevent biocrystallization of heme, thus causing heme toxicity to the parasite (Hempelmann 2007). In addition to antimalaria activity, chloroquine has the potential effects on other diseases, such as rheumatoid arthritis (Augustijns et al. 1992), lupus erythematosus (Meinao et al. 1996) and cancer (Solomon and Lee 2009). "
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    ABSTRACT: Despite standard cancer therapies such as chemotherapy and targeted therapy have shown some efficacies, the cancer in many cases eventually relapses and metastasizes upon stopping the treatment. There is a small subpopulation of cancer cells within tumor, with specific characters similar to those found in stem cells. This group of cancer cells is known as tumor-initiating or cancer stem cells (CSCs), which have an ability to self-renew and give rise to cancer cell progeny. CSCs are related with drug resistance, metastasis and relapse of cancer, hence emerging as a crucial drug target for eliminating cancer. Rapid advancement of CSC biology has enabled researchers to isolate and culture CSCs in vitro, making the cells amenable to high-throughput drug screening. Recently, drug repositioning, which utilizes existing drugs to develop potential new indications, has been gaining popularity as an alternative approach for the drug discovery. As existing drugs have favorable bioavailability and safety profiles, drug repositioning is now actively exploited for prompt development of therapeutics for many serious diseases, such as cancer. In this review, we will introduce latest examples of attempted drug repositioning targeting CSCs and discuss potential use of the repositioned drugs for cancer therapy.
    Archives of Pharmacal Research 07/2015; 38(9). DOI:10.1007/s12272-015-0628-1 · 2.05 Impact Factor
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    • "It is a non-toxic insoluble microcrystalline by-product formed by polymerizing free-toxic heme after digestion of haemoglobulin by Plasmodium and some other RBC-feeding parasites[10] [43] [44]. Several currently available antimalarial drugs including mefloquine and chloroquine act by blocking the haemozoin biocrystallization that kills malaria parasite[45]. Even though the exact process for formation of haemozoin is barely understood, the HRP2 is suggested to assist initiation of haemozoin formation by firmly binding to heme molecules and initiating their polymerization. "
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    ABSTRACT: Malaria remains as one of the significant health threat to people living in countries throughout tropical and subtropical zones. Proteomic studies of Plasmodium, the protozoan causing malaria, is essential for understanding its cellular structure, growth stage-specific expression of protein metabolites and complex interaction with host. In-depth knowledge of the pathogen is required for identification of novel biomarkers that can be utilized to develop diagnostic tests and therapeutic antimalarial drugs. The alarming rise in drug-resistant strains of Plasmodium has created an urgent need to identify new targets for drug development that can act by obstructing life cycle of this parasite. In the present review, we briefly discuss on role of various biomarkers including Plasmodium-associated aldolase, histidine-rich proteins and lactate dehydrogenase for diagnosis of malaria. Here we also summarize the present and future prospects of currently used techniques in proteomic approaches such as two dimensional gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) for diagnosis and potential identification of novel proteins for malaria research. Copyright © 2015 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.
    Asian Pacific Journal of Tropical Medicine 04/2015; 419(4). DOI:10.1016/S1995-7645(14)60327-8 · 0.93 Impact Factor
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    • "Research efforts are needed to find alternative treatments for malaria that avoid the problem of drug resistance altogether. One approach for the development of new treatments against malaria is to study the Plasmodium distinctive molecule hemozoin and to try to target this vital pathway of the parasite [5]. Hemozoin (HZ) is a metabolically crystallized byproduct of the digestion of hemoglobin by the parasite during infection of the red blood cells (RBCs). "
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    ABSTRACT: Background Malaria is an extremely devastating disease that continues to affect millions of people each year. A distinctive attribute of malaria infected red blood cells is the presence of malarial pigment or so-called hemozoin. Hemozoin is a biocrystal synthesized by Plasmodium and other blood-feeding parasites to avoid the toxicity of free heme derived from the digestion of hemoglobin during invasion of the erythrocytes. Scope of Review Hemozoin is involved in several aspects of the pathology of the disease as well as in important processes such as the immunogenicity elicited. It is known that the once best antimalarial drug, chloroquine, exerted its effect through interference with the process of hemozoin formation. In the present review we explore what is known about hemozoin, from hemoglobin digestion, to its final structural analysis, to its physicochemical properties, its role in the disease and notions of the possible mechanisms that could kill the parasite by disrupting the synthesis or integrity of this remarkable crystal. Major Conclusions The importance and peculiarities of this biocrystal have given researchers cause to consider it as a target for new antimalarials and to use it through unconventional approaches for diagnostics and therapeutics against the disease. General Significance Hemozoin plays an essential role in the biology of malarial disease. Innovative ideas could use all the existing data on the unique chemical and biophysical properties of this macromolecule to come up with new ways of combating malaria.
    Biochimica et Biophysica Acta (BBA) - General Subjects 06/2014; 1840(6). DOI:10.1016/j.bbagen.2014.02.009 · 4.38 Impact Factor
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