Design and study of novel chromone and thiochromone derivatives as PfLDH inhibitors — computational approach

Abstract

Malaria is one of the most neglected diseases in the South African countries, which leads to many deaths each year and the currently available drugs in the market are day-by-day acquiring resistance towards the plasmodium parasite. Hence, there is an immense need that arises to search for novel molecules to treat malaria. The Plasmodium falciparum lactate dehydrogenase (PfLDH) has been elected as the molecular target to check the binding affinity of the titled chromone and the thiochromone disubstituted analogous compounds. The molecular docking studies were done, which gave rise to the top two compounds (compounds 318 and 159), which were further subjected to in silico ADMET prediction and molecular dynamics study to observe the molecule’s behavior. The in silico-predicted SAR was derived for the designed compounds based on their predicted inhibitory constants. The output of the study reveals that the chromone and thiochromone analogs may emerge as potential agents against malaria and further studies need to be performed.