Publication

Abstract : Malaria control remains a challenge, especially in countries where a large population lives in poverty. Conventionally, quinolines like quinine, chloroquine, and mefloquine have been used for treating malaria for many years. However, Plasmodium falciparum, the Malaria parasite widely prevalent in African countries, reportedly resisted CQ. Reportedly, the K76T mutation in the pfcrt gene (plasmodium falciparum chloroquine resistance transporter) has been responsible for CQ-related resistance. Studies suggest that the mutated protein product of the gene allows the chloroquine to escape from the vacuole in an energy-independent process, causing resistance. Because lactate dehydrogenase (LDH) plays a vital role in the carbohydrate metabolism in plasmodium, it can be considered a suitable target for drug design strategies. In the current study, a series of chloroquine derivatives, namely, Hydroxychloroquine-o-acetate (compound 1), 4-((7-chloroquinoline-4-amino) penta-1-ol (compound 2), Bis-desethylchloroquine (compound 3) were selected for preliminary investigation as anti-plasmodial drugs. The optimized geometry corresponding to the global minimum energy was predicted using density functional theory and Gaussian 03 software. The optimized geometries were then subjected to molecular docking studies against Pf-LDH using CHIMERA software to assess their suitability as anti-plasmodial agents. The bioavailability of these compounds was evaluated by computationally assessing features such as absorption, distribution, metabolism, extraction, and toxicity. Insights into the drug-likeness of the select compounds were also analyzed by computing physiochemical parameters like topological polar surface area, lipophilicity, blood-brain barrier, etc.