Antimalarial pharmacodynamics of chalcone derivatives in combination with artemisinin against Plasmodium falciparum in vitro

Use of artemisinin based combination therapies (ACTs) is increasing in treatment of malaria. Their extensive and indiscriminate deployment will ultimately lead to selection of resistance. Thus, alternate ACTs are needed. We reported in vitro antimalarial potential of chalcone derivatives. A few potent chalcones were selected for their antimalarial interaction in combination with artemisinin in vitro. Combinations evaluated show synergistic or additive interactions. Chalcones act on broad range of asexual stages of the parasite. The synergistic combinations decrease hemozoin formation in parasitized erythrocytes. These combinations do not affect new permeation pathways induced in the host cells. This is the first report showing antiplasmodial interactions between artemisinin and synthetic chalcone azole derivatives. Thus, chalcones and artemisinin combinations open the possibility of novel ACTs.

Earlier we reported synthesis of novel azole-chalcone derivatives with antiplasmodial activity in vitro. Here we report antimalarial interaction of artemisinin in combination with each of the three most potent chalcones.Figure optionsDownload as PowerPoint slideSK1) R1 = H, R2 = Cl, R3 = HSK2) R1 = H, R2 = Cl, R3 = HSK7) R1 = H, R2 = Cl, R3 = H(a) Cyclic amines, K2CO3, DMF, 18 h, 110 °C(b) NaOH, methanol, 16–20 h, rt.