This study examines the reactivity of an intramolecular cyclization process involving benzastatin, a molecule derived from Streptomyces nitrosporeus, using density functional theory (DFT) with the B3LYP functional and the 6-311G(d,p) basis set. Parr indices, calculated by natural bond orbital (NBO) analysis, provide insight into the reactivity and chemical behavior of the system. In addition, the electron localization function (ELF) is used to analyze bond formation during the process. A molecular docking study highlights the pharmacological potential of benzastatin-derived alkaloids against Plasmodium falciparum, the malaria parasite, by targeting the key enzymes falcipain-2 and falcipain-3. The study elucidates the key interactions and binding affinities between the reaction products involved and these enzymes, supported by molecular dynamics simulations to study the stability of the ligand-protein complex over 50 ns. ADMET predictions suggest favorable pharmacokinetic profiles and low toxicity for the compounds, underlining their potential as antimalarial drug candidates.
