The quinolinyl chalcones series (A_{1}-A_{14}) were screened for antimalarial activity. According to in vitro antimalarial studies, many quinolinyl chalcones are potentially active against CQ-sensitive and resistance P. falciparum strains with no toxicity against Vero cell lines. The most active quinolinyl chalcones A_{4} (with IC_{50} 0.031 μM) made a stable A_{4}-heme complex with – 25 kcal/mole binding energy and also showed strong π-π interaction at 3.5 Å. Thus, the stable A_{4}-heme complex formation suggested that these quinolinyl chalcones act as a blocker for heme polymerization. The docking results of quinolinyl chalcones with Pf-DHFR showed that the halogenated benzene part of quinolinyl chalcones made strong interaction with Pf-DHFR as compared to quinoline part. A strong A_{4}-Pf-DHFR complex was formed with low binding energy (- 11.04 kcal/mole). The ADMET properties of quinolinyl chalcones were also studied. The in vivo antimalarial studies also confirmed the A_{4} as an active antimalarial agent.
【저자키워드】 antimalarial, acetophenone, Pf-DHFR, Heme binder, Quinolinyl chalcones,