Heme aggregation inhibitors

HEME AGGREGATION INHIBITORS ANTIMALARIAL DRUGS TARGETING AN ESSENTIAL BIOMINERALIZATION PROCESS... 

Most of the reported in vivo data presented in the literature involves the infection of donor mice with a strain of P. berghe [61]. After a parasitemia of circa 30% is achieved in the donor mice, a blood sample is taken, diluted, and injected into experimental and control mice. The parasitemia load is regularly monitored for 3 to 7 days after infection by blood smear analysis as a function of drug dose. While in vivo efficacy assays reveal the true scope of a potential antimalarial s efficacy, the methods are very expensive. Consequently, additional assays have been developed to rapidly assess the effectiveness of lead heme aggregation inhibitors. 

Ziegler J, Linck R, Wright DW. Heme aggregation inhibitors antimalarial drugs targeting an essential biomineralization process. Curr. Med. Chem. 2001 8 171-189. 

As is often the case in multidisciplinary research, a number of different assays have been developed to monitor the inhibition of hemozoin aggregation (Table 1). Consequently, a great deal of confusion has arisen in the literature concerning the exact efficacy of a particular hemozoin inhibitor. For this reason, it is worthwhile to discuss the principal assays employed in the evaluation of antimalarial compounds and those assays specifically designed to evaluate heme aggregation inhibition. 

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