IN SILICO APPRAISAL OF AZETIDINE, 1,2-DIMETHYL (SOLCITINIB) BINDING WITH TUMOR NECROSIS FACTOR- Α AND INTERLEUKIN 6

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. The aim of this study was to investigate the potential anti-inflammatory effects of Azetidine, 1,2-dimethyl (Solcitinib) in combination with Terminalia catappa extract on Tumor Necrosis Factor-alpha (TNF-α) and Interleukin 6 (IL-6) in treatment of obesity. 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. This study employed virtual screening to identify potential bioactive compounds from Terminalia catappa nuts that exhibit high binding affinity against the protein target 1ALU. The results revealed that Azetidine, 1, 2 – dimethyl (CID_11626560) demonstrated the highest binding affinity, with docking scores of -7 and -8 against PDB 1ALU, when interacting with TNF-α and IL-6, respectively. Post-docking analysis revealed that CID_11626560 exhibited well-defined binding pockets, characterized by pi-alkyl bonds and hydrogen bonding with residues Valine-93 and Proline-154 (Fig 2A and 2B). Additionally, CID_11626560 displayed van der Waal, alkyl, and pi-alkyl bonds with residues Glucine-172, Alanine-68, Lysine-86, Proline-65, Leucine-64, and Arginine-168. In conclusion these findings suggest that Azetidine, 1, 2 – dimethyl, a compound derived from Terminalia catappa nuts, may possess potential anti-inflammatory properties by targeting TNF-α and IL-6.