A quantum mechanical study of novel potential inhibitors of cytochrome bc1 as antimalarial compounds

Cytochrome bc1 is a validated drug target of Plasmodium falciparum, the parasite that causes the most lethal form of malaria. The inhibition of cytochrome bc1 leads to the shutdown of the mitochondrial metabolism and the consequent arrest of pyrimidine biosynthesis essential for parasite development. Aiming to rationalize the stereoelectronic properties and extend the knowledge on a novel series of 4-pyridonimines guiding the search of antimalarial drugs, we carried out an extensive DFT comparative characterization. Results show electronic similarity with clopidol, a known bc1 complex inhibitor containing the 4(1H)-pyridone scaffold.

Tiago Rodrigues, Daniel J. V. A. dos Santos, Rui Moreira, Francisca Lopes, Rita C. Guedes

iMed.UL, Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-019 Lisbon, Portugal

http://dx.doi.org/10.1002/qua.22741

 

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