Alkaloids from Pandanus amaryllifolius Roxb Leaf as Promising Candidates for Antidyslipidemic Agents: An in silico study

Introduction: The plant Pandanus amaryllifolius Roxb (pandan), has been shown to have antidyslipidemic potency. This study explored the potential of several alkaloids from pandan leaf as antidyslipidemia as well as their safety profile in silico. Methods: Analyses were carried out by studying the binding affinity of the alkaloids to 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, peroxisome proliferator activator receptor (PPAR) alpha and Niemann Pick C1 Like 1 (NPC1L1). The structures of the alkaloids were downloaded from the Pubchem database and optimized using the ChemDraw Professional 16.0 to obtain 3D structures in protein data bank (PDB) format. The in silico testing was based on the interactions of the alkaloids with the HMG-CoA reductase (PDB ID 1HW9), PPAR alpha (PDB ID 6LX4) and NPC1L1 (PDB ID 7DFZ) proteins, downloaded from the Research Collaboratory for Structural Bioinformatics (RSCB) PDB website (http://www.rcsb.org/pdb). The preparation of protein structures was performed using the Discovery studio 2021 client and Gromacs applications, while optimization of the 3D structure of the alkaloids was carried out with the ChemDraw professional 16.0. Finally, validation was completed using AutoDock application. The safety profile was assessed by pkCSM online tool. Results: The respective root mean square deviation (RMSD) values of the 1HW9, 6LX4 and 7DFZ proteins were 1.677, 0.918 and 1.706, respectively. The alkaloids pandanusine B, pandamarilactonine A, pandamarilactonine B had respective values of binding energy for HMG-CoA of -5.52, -5.51 and -5.46 kcal/mol. The binding energy of pandamarilactonine B, pandamarilactonine A and pandanamine for PPAR alpha were -9.14, -9.10 and -8.48 kcal/mol, respectively, with the corresponding energy for t NPC1L1 of -9.63, -9.71 and -8.54 kcal/mol. The toxicity tests indicated that the alkaloids were safe, pandamarilactonines had the highest LD50 (2.736 mol/ kg). Conclusion: The studied pandan alkaloids have potential antidyslipidemic activity by interacting with HMG-CoA reductase, PPAR alpha, and NPC1L1, with good safety profile.