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.