Journal
PROCESSES
Volume 10, Issue 11, Pages -Publisher
MDPI
DOI: 10.3390/pr10112443
Keywords
malaria; Plasmodium knowlesi; lactate dehydrogenase; virtual screening; inhibition assay
Categories
Funding
- International Islamic University Malaysia Research Initiative Grants [RIGS15-141-0141]
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Malaria management remains challenging due to drug resistance. This study identified two potential antimalarial drugs through virtual screening analysis, which showed inhibitory effects against Pk-LDH. Further exploration and development of the compound oxalic acid may lead to a promising antimalarial drug for P. knowlesi infection.
Malaria management remains a challenge, due to the resistance of malaria parasites to current antimalarial agents. This resistance consequently delays the global elimination of malaria throughout the world. Hence, the demand is increasing for new and effective antimalarial drugs. The identification of potential drugs that target Pk-LDH can be obtained through virtual screening analyses, as this has been previously applied to discover Pf-LDH inhibitors. In this study, the selected candidates from our virtual screening analyses were subsequently tested against purified Pk-LDH, and verified through an inhibition of Pk-LDH via enzymatic activity assays. Virtual screening analysis from this study showed that 3,3-Difluoropyrrolidine hydrochloride and 3-hydroxytetrahydrofuran exhibited binding affinity values of -3.25 kcal/mol and -3.74, respectively. These compounds were selected for evaluation towards inhibitory activity against Pk-LDH assays, including two compounds from a previous study which are oxalic acid and glycolamide. The earlier compounds were structurally similar to lactate and pyruvate, and the latter two compounds were structurally similar to a known LDH inhibitor, oxamate. Among all of the compounds tested, oxalic acid showed the highest inhibition activity at 54.12%; interestingly, this correlated well with the virtual screening analyses, which showed that this compound was the best among the oxamate analogues, with a binding affinity value of -2.59 kcal/mol. Hence, further exploration and development of this compound may result in a promising antimalarial drug for malaria treatment, especially for infection involving P. knowlesi.
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