engleski

Antimalarial activity of novel amide-type harmicines

Malaria is a parasitic infectious disease responsible for more than 400 000 deaths annually [1]. The increasing multidrug resistance of Plasmodium falciparum, the most deadly human malaria pathogen, poses a major threat to global efforts to control malaria [2]. One of the promising strategies being pursued to overcome the emergence of resistant parasite strains is the development of hybrid compounds, in which two or more pharmacophores are combined into a single molecule. Harmine is a β-carboline alkaloid and a potent inhibitor of Plasmodium falciparum heat shock protein 90 (PfHsp90). On the other hand, covalent binding of cinnamic acid derivatives (CADs) to the known antimalarial drugs results in increased antimalarial activity [3]. Considering all these aspects, novel hybrid compounds composed of harmine and CADs, i.e. harmicines (Figure 1.) have been prepared and evaluated for in vitro antimalarial activity. Both N-harmicines (5a-f) and O-harmicines (6a-h) exerted remarkable activity against the erythrocytic stage of P. falciparum. The highest activity exerted N- harmicine 5e with IC50 values in low submicromolar range (0.04 μM for Pf3D7 strain and 0.17 μM for the PfDd2 strain).

malaria, harmine, cinnamic acid derivatives, antimalarial activity, harmicines

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