IN SILICO STUDY OF PYRIMIDINARYLTELLURIDES AS POTENTIAL INHIBITORS OF PLASMODIUM FALCIPARUM

Malarial plasmodia are increasingly developing resistance to existing antimalarial drugs, posing a serious threat to successful treatment. Previous studies have demonstrated the inhibitory activity of compounds containing an exocyclic aryltellurium fragment against Plasmodium falciparum. This research focused on evaluating the inhibitory potential of fused pyrimidinaryl tellurides against falcipain-2 (FP-2), a crucial therapeutic target in the fight against malaria. Among the tested tellurides, 2-(((4-methoxyphenyl)thelanyl)methyl)-2,3-dihydro-5H-thiazolo[2,3-b]quinazolin-5-one demonstrated the most stable protein-ligand complex with the receptor 2GHU. The ligand exhibited a binding energy of -6.18 kcal/mol and an inhibition concentration of 29.74 μM. Notably, the ligand interacted with specific amino acids of the receptor, including HIS27, ASP23, TYR199, LYS184, and ALA21. Additionally, a 100 ns molecular dynamics study confirmed the stability of the falcipain-2 complex with this thiazoloquinazolinaryltellurtrichloride, further supporting the potential of compound 1. Importantly, the tested substance exhibited superior inhibitory capability against Plasmodium falciparum compared to antimalarial drugs such as mefloquine, primaquine, and chloroquine, making it a candidate for in vitro evaluation of antimalarial activity. Keywords: malaria; Plasmodium falciparum; telluride; Falcipain-2; 2GHU.