Computational simulations of phytoconstituents derived from Phyllanthus amarus against Plasmodium falciparum molecular targets

Abstract

There has been an increase in the resistance of plasmodium parasites to already available malaria prevention drugs. Hence, the need for novel malaria-preventive medications. This study identified potential antiplasmodial drug candidates from Phyllanthus amarus. The phytoconstituent of Phyllanthus amarus was discovered using the Indian Medicinal Plants, Phytochemistry and Therapeutics Database as well as Dr Duke's phytochemical and ethnobotanical databases. The compounds were screened for ADMET properties and docked with five validated drug targets of Plasmodium falciparum using PyRx software. The molecular dynamics of the best complexes were simulated using Desmond software. A total of 54 compounds were retrieved for Phyllanthus amarus from the databases. Out of the 54 compounds, 26 were druggable, of which the majority showed a good ADMET profile. Amarulone -P. falciparum thioredoxin reductase (4b1b), Amarulone -P. falciparum enoyl-acyl carrier protein Reductase, Amariin-4b1b and Amarulone -Plasmodium falciparum lactate dehydrogenase (1u5c) complexes had the lowest binding energies of -12.3, -11.6, -11.3 and -11.2 kcal/mol, respectively. Amarulone-1u5c complex showed the lowest average RMSD value of 1.86 and 2.02 Å for the heavy backbone and protein-ligand complex, respectively. This makes the complex the most stable complex. Hence, further research should be done on Amarulone as a malaria drug candidate.