Active compound profiling in fraction 49 of a secondary metabolite extract from Streptomyces hygroscopicus subsp. Hygroscopicus as antimalaria drug using LCMS, molecular docking, and molecular dynamics

Background Antimalarial resistance in Indonesia is caused by mutations at the drug target sites and biochemical changes in drug receptors. Previous research indicates that only fraction 49 of Streptomyces hygroscopicus Subsp. Hygroscopicus (S. hygroscopicus) is effective as an antimalarial agent in in vitro tests. Methods The active compounds of secondary metabolites from S. hygroscopicus were identified using LCMS. The binding of compounds to target proteins (PfK13, PfPM2, and PfAMA-1) underwent molecular dynamic simulations to estimate the stability and flexibility of the binding through the dynamic structure of the molecules. Results The LCMS analysis identified four compounds with the fastest retention times (indicating increased non-polarity): Dibutyl phthalate, Dihydroyashabushiketol, Dibenzylamine, and Sedanolide. These compounds meet drug-likeness criteria (Lipinski’s rule and Veber’s rule) and exhibit binding affinity values similar to the control for each target protein. Hydrogen and hydrophobic bonds formed between the compounds and targets show similarities with the bonds formed between the target proteins and their respective control ligands. The stability and flexibility of the molecular structures of the active compounds were assessed using molecular dynamics. Dihydroyashabushiketol exhibited the highest binding affinity and demonstrated a stable and flexible structure toward the target proteins PfK13 and PfAMA-1. Conclusion Dihydroyashabushiketol exhibits the highest binding affinity values in almost all target proteins compared to the other compounds, suggesting that Dihydroyashabushiketol has the potential as an antimalarial agent. The compound demonstrates a stable and flexible structure towards the target proteins PfK13 and PfAMA-1, but not towards the PfPM2 protein.