Molecular Docking Studies of the Interaction of 1h-Pyrazol-4-Amine(crizotinib) and Azetidine, 1,2-Dimethyl(solcitinib) With Lysine Specific Demethylase

ABSTRACT Molecular docking studies are pivotal in modern drug discovery and development, offering insights into how small molecules interact with target proteins at the atomic level.This work is targeted to source for drug-like candidates that can be used for the treatment of sickle cell disease. In the present study, a total of twenty (20) compounds derived from Terminalia catappa nuts were screened by molecular docking against hydroxyurea. Out of the 20 screened compounds, 2 (namely; Azetidine, 1, 2 – dimethyl and1H - pyrazol 4 – amine) emerged as top pose compounds. Azetidine, 1, 2 – dimethyl and1H - pyrazol 4 – amine showed the most drug-like characteristics and overall; 1H - pyrazol 4 – amine had the most favorable characteristics. Some molecular docking studies reported Azetidine, 1, 2 – dimethyl and1H - pyrazol 4 – amine as top pose compounds of Terminalia catappa nuts with the strongest interactions against hydroxyurea. The reports showed that Azetidine, 1, 2 – dimethyl had a moderate affinity for the target while 1H - pyrazol 4 – amine was better. The present study however revealed that Azetidine, 1, 2 – dimethyl and1H - pyrazol 4 – amine are the ligands with superior drug-like characteristics. Azetidine, 1, 2 – dimethyl only showed a moderate binding affinity (docking score of -8.8) whereas 1H - pyrazol 4 – amine had showed a high binding affinity (docking score of -9.9) in the present study. About twenty (20) compounds derived from Terminalia catappa nuts (Table 1) were screened against 3657, in which two (2) top posed compounds exhibited the highest binding affinities against the protein target and were selected for post docking analysis. From the multiple screening analysis, the following compounds Azetidine, 1, 2 – dimethyl (CID_ 11626560) and 1H - pyrazol 4 – amine (CID_ 44603362), showed the lowest docking scores (highest binding affinity scores) of -8.8 and-9.9 respectively against PDB 3657. This virtual screening based on binding energy gave us a vivid idea of the best ligands having the highest affinity for PDB 3657.