In Silico Drug Discovery: Unveiling Potential Targets in Plasmodium falciparum through Molecular Docking Analysis

The most significant human health problem is malaria, caused by the Plasmodium parasite and affecting nearly half of the global population. Malaria results in an annual death toll ranging from 1.2 to 2.7 million worldwide. Consequently, there is a pressing need for novel active ingredients with targeted effects to curb the worldwide spread of malaria. The objective of the present research was to explore innovative pharmacological molecules and employ bioinformatics methods for the development of effective anti-malarial drugs. As part of the latest anti-malarial chemical development, our study identified seven drug combinations from various databases demonstrating drug-like properties and robust anti-malarial activity in silico . Dioncophyllin-A, hugorosenone, marmesine, oxyprotostemonin, pachyrrhizin, plumbagin, and stemocurtisin were subjected to docking against the hexokinase-1 protein (PDB: 1CZA). Among the pachyrrhizin compounds, the one with the highest docking score (-9.9 kcal/mol) was directed towards the 1CZA protein. Through superimposing the target and template structures, the active centres of the hexokinase I protein were identified, revealing structurally identical folds and undoubtedly conserved active sites. The SWISS-ADME tool was employed to assess the excellent absorption, distribution, metabolism, and excretion (ADME) properties of the investigated drug candidates. In summary, our research identifies seven potential anti-malarial drug combinations with strong in silico activity. We've elucidated their interaction with the hexokinase-1 protein and assessed their favourable pharmacokinetic properties. These findings represent a significant step toward developing effective treatments for malaria, emphasizing the importance of further experimental validation and clinical studies.