Infectious disorders drug targets · 2026
Antimalarial Candidate Study from Three Different Fractions of Streptomyces hygroscopicus subsp. Hygroscopicus targeting Plasmodium DXR: An In Silico Approach.
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Faratisha Icha Farihah Deniyati, Fitri Loeki Enggar, Winaris Nuning, Widodo Nashi
Аннотация
INTRODUCTION: The use of natural products is one approach in the discovery of new antimalarial drugs. Previous research has identified several compounds in crude extracts and fractions of Streptomyces hygroscopicus subsp. hygroscopicus that exhibit antimalarial properties. Protein targets in Plasmodium are similarly being investigated, including 1-deoxy-D-Xylulose-5-phosphate Reductioisomerase (DXR) from the Methyl Erythritol Phosphate (MEP) pathway of the apicoplast organelle, which is unique to Plasmodium, and thus an interesting target. The purpose of this study was to identify compounds from fractions 13, 50, and 51 of Streptomyces hygroscopicus subsp. hygroscopicus using Liquid Chromatography/High Resolution Mass Spectrometry (LC/HRMS) and examine antimalarial potential using an in silico approach.
METHODS: The compounds from fractions 13, 50, and 51 were identified using LC/HRMS and continued with pharmacokinetic (Swiss ADME) and toxicity prediction (Protox 3.0). The DXR protein was downloaded from the Protein Data Bank (PDB ID: 3AU9). Molecular docking and interaction were performed using Autodock Vina (PyRx 0.9), LigPlot, and PyMOL. Molecular dynamic simulation was performed with YASARA (version 19.14.12).
RESULTS: 18, 24, and 44 compounds were identified from fractions 13, 50, and 51, respectively, of which 9 were selected for their potential antimalarial properties. All compounds met drug-likeness criteria, and only two had acceptable toxicity profiles. Molecular docking studies revealed that dibenzylamine (fraction 13 and 50) and erucamide (fraction 51) exhibited higher binding affinity to DXR than the native ligand. Molecular dynamics simulation for 100 ns revealed that the erucamide-DXR complex was more stable than dibenzylamine or the native ligand.
DISCUSSION: These findings suggest that erucamide, a metabolite compound identified from Streptomyces hygroscopicus subsp. hygroscopicus, may potentially interact with the DXR enzyme of the MEP pathway. While the computational results provide preliminary insight into its possible antimalarial activity, these predictions should be interpreted cautiously. However, further in vitro and in vivo validation is essential to confirm its efficacy and safety. This study emphasizes the potential of compounds produced from natural products for novel antimalarial treatment.
CONCLUSION: The erucamide compound demonstrated the highest binding affinity and a more stable molecular interaction with the DXR protein.
METHODS: The compounds from fractions 13, 50, and 51 were identified using LC/HRMS and continued with pharmacokinetic (Swiss ADME) and toxicity prediction (Protox 3.0). The DXR protein was downloaded from the Protein Data Bank (PDB ID: 3AU9). Molecular docking and interaction were performed using Autodock Vina (PyRx 0.9), LigPlot, and PyMOL. Molecular dynamic simulation was performed with YASARA (version 19.14.12).
RESULTS: 18, 24, and 44 compounds were identified from fractions 13, 50, and 51, respectively, of which 9 were selected for their potential antimalarial properties. All compounds met drug-likeness criteria, and only two had acceptable toxicity profiles. Molecular docking studies revealed that dibenzylamine (fraction 13 and 50) and erucamide (fraction 51) exhibited higher binding affinity to DXR than the native ligand. Molecular dynamics simulation for 100 ns revealed that the erucamide-DXR complex was more stable than dibenzylamine or the native ligand.
DISCUSSION: These findings suggest that erucamide, a metabolite compound identified from Streptomyces hygroscopicus subsp. hygroscopicus, may potentially interact with the DXR enzyme of the MEP pathway. While the computational results provide preliminary insight into its possible antimalarial activity, these predictions should be interpreted cautiously. However, further in vitro and in vivo validation is essential to confirm its efficacy and safety. This study emphasizes the potential of compounds produced from natural products for novel antimalarial treatment.
CONCLUSION: The erucamide compound demonstrated the highest binding affinity and a more stable molecular interaction with the DXR protein.