Antimalarial and β-hematin formation inhibitory activities of chromone derivatives

Abstract

A series of chromone derivatives were evaluated as antimalarial and β-hematin formation inhibitory activities. The in vitro antimalarial activity was evaluated using the microculture radioisotope assay. The three most potent antimalarial compounds were 34, 36 and 39 with IC50 = 3.82, 0.95 and 4.87 μM, respectively. Compound 36, the most active, showed higher potency than primaquine and tafenoquine. For β-hematin formation inhibitory activity assay, the top six most potent compounds, 23-28 (IC50 = 1.41, 1.76, 2.30, 2.54, 4.60 and 3.69 μM, respectively) were more potent than chloroquine, dihydroartemisinin, and mefloquine. The ability of chromone compounds to interact and form complex with heme was investigated by the continuous variation technique (Job’s plot). Compounds 28, 38 and 42 interacted with heme with stoichiometric ratio of chromone:heme = 1:1, same ratio as dihydroartemisinin. Compounds 3, 4, 23, 24, 27 and 43 showed the stoichiometric ratio = 1:2, same as chloroquine and mefloquine and compound 36 showed stoichiometric ratio = 1:3.