Synthesis, structural characterization of novel Coumarin derivatives aspotential antimalarial agents

[摘要] A series of new Coumarin derivatives of aldehydes was synthesized and tested against Plasmodium falciparum strains. Ten new Coumarin analogues showed significant activity in the nano molar range (IC50 = 90–186 nm) against Plasmodium falciparum CQ-resistant strain FcB1. A possible mechanism of interaction implicating binding of these compounds to b-hematin was supported by in vitro tests. Moreover, the importance of the hydrophilic framework attached at the terminal nitrogen atom of the Coumarin and aldehyde joined to the chalcone ring was also explored through molecular dynamic simulations. Seven of the analogues (SS01, SS02, SS03, SS06, SS07, SS09, SS10) have exhibited curative antimalarial activity at a dose of 25mg/kg/day×4 and produced suppressive activity at a lower dose of 10 mg/kg/day×4The results of antimalarial activity showed that the ligand SS-01, SS02 exhibits moderately active while complex SS-06, SS09 exhibits good activity for chloroquine sanstive and resistant.

[学科分类] 药理学