Identification of new antimalarial leads by use of virtual screening against cytochrome bc1
Cytochrome bc1 is a validated drug target in malaria parasites. The spread of Plasmodium falciparum strains resistant to multiple antimalarials emphasizes the urgent need for new Identification of new antimalarial leads by use of virtual screening against cytochrome bc1drugs. We screened in silico the ZINC and MOE databases, using ligand- and structure-based approaches, to identify new leads for development. The most active compound presented an IC50 value against cultured P. falciparum of 2 μM and a docking pose consistent with its activity.
Tiago Rodrigues a, Rui Moreira a, Jiri Gut b, Philip J. Rosenthal b, Paul M. O0Neill c, Giancarlo A. Biagini d, Francisca Lopes a, Daniel J.V.A. dos Santos a, Rita C. Guedes a
a Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-019 Lisbon, Portugal
b Department of Medicine, San Francisco General Hospital, University of California, San Francisco, Box 0811, San Francisco, CA 94143, USA
c Department of Chemistry, University of Liverpool, Crown Street, Liverpool L69 7ZD, United Kingdom d Molecular and Biochemical Parasitology, Liverpool School of Tropical Medicine, University of Liverpool, Liverpool L3 5QA, United Kingdom
http://dx.doi.org/10.1016/j.bmc.2011.09.004