In-silico identification of sulfur and selenium analogous to artemisinin as potential antimalarial drug candidates

Abstract

Malaria continues to be a significant global health challenge, with approximately two million deaths annually. The emergence of resistance to potent artemisinin derivatives in existing drugs and combination therapies has heightened the need for novel antimalarial compounds. To address this issue, we conducted a comprehensive molecular docking and pharmacokinetic study on artemisinin-based compounds to identify potential candidates against Plasmodium falciparum, a deadly malaria parasite. We screened 30 molecules of sulfur and selenium-substituted artemisinin and subjected them to docking and pharmacokinetic analysis, followed by molecular dynamics simulation. Drug-likeness, ADME properties, and toxicity analysis were performed to evaluate their pharmacological potential. Seven compounds emerged as potent antimalarial agents. Further molecular dynamics simulations revealed that five of these compounds formed stable complexes and exhibited strong binding to the target’s active site pocket, supported by structure–activity relationships. Notably, among the screened molecules, the disulfide analogous to artemisinin demonstrated superior potency compared to artemisinin, displaying low toxicity, extended half-life, reduced clearance, and potent inhibition properties.