Antimalarial Activity of Natural Products Against Plasmodium Lactate Dehydrogenase Screened by Molecular Docking

Malaria is a parasitic disease which causes high mortality and morbidity rates all over the world. This disease is caused by four species of plasmodium: P. vivax, P. malariae, P. ovale and P. falciparaum. The enzyme lactate dehydrogenase (LDH) catalyses the interconversion of L-lactate and pyruvate with the interconversion of NAD+ as a cofactor. This enzyme is a possible new target to be exploited in the development of new antimalarial agents. Three X-ray structures of lactate dehydrogenase of plasmodium spp. were downloaded from protein data bank. A total of 120 natural products belongs to flavonoids, alkaloids, anthraquinones, coumarins, lignans, chalcones and iridoids were screened in silico against LDH. Molecular docking was performed by Hex 8.0.0 using NAD+ as a positive control. Magnoloside A had the highest binding affinities in terms of the total interaction energy in Kcal/mol. Eight analogs of magnoloside A were also sketched by ChemBioDraw Ultra 11.0. Analog-7 (fouro-substituted) and analog-8 (Bromo and chloro substituted) had higher binding affinities than that of NAD+. Therefore, magnoloside A and its halogenated analogs, rutin, amentoflavone, and hinokiflavone might be useful in the experimental design of anti-malarial agents.