4ige

Publication Abstract from PubMed

Malaria, a disease of worldwide significance, is responsible for over one million deaths annually. The liver-stage of Plasmodium's life cycle is the first, obligatory, but clinically silent step in malaria infection. The P. falciparum type II fatty acid biosynthesis pathway (PfFAS-II) has been found to be essential for complete liver-stage development and has been regarded as a potential antimalarial target for the development of drugs for malaria prophylaxis and liver-stage eradication. In this paper, new coumarin-based triclosan analogues are reported and their biological profile is explored in terms of inhibitory potency against enzymes of the PfFAS-II pathway. Among the tested compounds, 7 and 8 showed the highest inhibitory potency against Pf enoyl-ACP-reductase (PfFabI), followed by 15 and 3. Finally, we determined the crystal structures of compounds 7 and 11 in complex with PfFabI to identify their mode of binding and to confirm outcomes of docking simulations.

Design, Synthesis, and Biological and Crystallographic Evaluation of Novel Inhibitors of Plasmodium falciparum Enoyl-ACP-reductase (PfFabI).,Belluti F, Perozzo R, Lauciello L, Colizzi F, Kostrewa D, Bisi A, Gobbi S, Rampa A, Bolognesi ML, Recanatini M, Brun R, Scapozza L, Cavalli A J Med Chem. 2013 Oct 10;56(19):7516-26. doi: 10.1021/jm400637m. Epub 2013 Sep 25. PMID:24063369^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.