antimalarial activity of potential inhibitors of plasmodium falciparum lactate dehydrogenase enzyme selected by docking studies抗疟活性的潜在的恶性疟原虫乳酸脱氢酶酶抑制剂被对接研究.pdfVIP

Antimalarial Activity of Potential Inhibitors of Plasmodium falciparum Lactate Dehydrogenase Enzyme Selected by Docking Studies 1,2 3 3 Julia Penna-Coutinho , Wilian Augusto Cortopassi , Aline Alves Oliveira , Tanos Celmar Costa Franc¸a3*, Antoniana Ursine Krettli1,2* ´ ´ ´ 1 Faculdade de Medicina, Universidade Federal de Minas Gerais, (UFMG), Belo Horizonte, Minas Gerais, Brazil, 2 Laboratorio de Malaria, Centro de Pesquisas Rene Rachou, FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil, 3 Laboratory of Molecular Modeling Applied to the Chemical and Biological Defense (LMCBD), Military Institute of Engineering, Rio de Janeiro, Rio de Janeiro, Brazil Abstract The Plasmodium falciparum lactate dehydrogenase enzyme (PfLDH) has been considered as a potential molecular target for antimalarials due to this parasite’s dependence on glycolysis for energy production. Because the LDH enzymes found in P. vivax, P. malariae and P. ovale (pLDH) all exhibit ,90% identity to PfLDH, it would be desirable to have new anti-pLDH drugs, particularly ones that are effective against P. falciparum, the most virulent species of human malaria. Our present work used docking studies to select potential inhibitors of pLDH, which were then tested for antimalarial activity against P. falciparum in vitro and P. berghei malaria in mice. A virtual screening in DrugBank for analogs of NADH (an essential cofactor to pLDH) and computational studies were undertaken, and the potential binding of the selected compounds to the PfLDH active site was analyzed using Molegro Virtual Docker software. Fifty compounds were selected based o