In-silico drug discovery of two Novel Losartan based Kojic acid derivatives against BCL-2 Protein for the treatment of Leukemia

Background : Current research was conducted to investigate novel kojic acid derivatives based on losartan as potential leukemia treatment options. Furthermore, this study examined the affinity of the connection to binding with BCL2 protein, one of the targets of leukemia identified. Methods and Materials: The kojic acid derivatives reported with losartan were manufactured using ChemDAW 2022 software and examined according to high-positive drug complication values. DisGeNET algorithm was used to further predict targets where connections with high drug-like assessments were likely, and strings were used to assess interactions between altered proteins. The KEGG Pathway database was used to document the relevant paths. The efficiency of binding between the losartan-based BCL2 protein and the coordinate derivative was ultimately assessed by PyrX by docking. To observe interactions between the ligand and protein, ligands were selected with the lowest binding energy score. Molecular dynamic GROMACS simulations were used to assess the kinematics and stability of the top protein league complex. Results: Three compounds were found to have the greatest drug likeness ratings. These compounds regulated a number of pathways linked to leukemia. Using GROMACS Molecular Dynamic Simulation analysis and molecular docking, one molecule with the best anti-leukamia potentials was ultimately identified. With BCL2 protein, the docking sores of a single chemical, 3-(4'-((2-butyl-4-chloro-5-(hydroxymethyl)-1H-imidazol-1-yl) methyl)-[1,1'-biphenyl]-2-yl)-5-hydroxy-2-methyl-4H-pyran-4-one (Comp2), are -8.4 kcal/mol. Conclusion: Docking analysis showed that, 3-(4'-((2-butyl-4-chloro-5-(hydroxymethyl)-1H-imidazol-1-yl) methyl)-[1,1'-biphenyl]-2-yl)-5-hydroxy-2-methyl-4H-pyran-4-one (Comp2) had the strongest affinity for binding the BCL2 protein, and all protein-ligand complexes were determined to be stable upon performing a GROMACS Molecular Dynamic Simulation.