Discovery of lophine derivatives as multi-targeting agents: A computational approach

Shyamal Kumar Biswas, Akash Koley, Rimpa Jana, Jagrity Biswas

Article Under Review

Lophine is one of the new core moiety with substitution of three phenyl rings at 2nd, 4th, and 5th position of the imidazole. Lophine is not explored in development of drug molecules. In this research, we have designed 30 lophine derivatives with different substituted functional groups. The designed compounds were evaluated through different in-silico tools and softwares to check their properties for different biological receptors. Molecular docking study was carried out on different receptors i.e. EGFR for anti-cancer, COX-1, and COX-2 for anti-inflammatory, fungal oxidoreductase for anti-fungal, bacterial DNA gyrase for anti-bacterial and TNF-α, which co-relates different type of inflammatory diseases. The molecular docking results revealed that the SAP-28 has significant binding energies -9.8, -9.6 and -10.0 kcal/mol against EGFR, fungal oxidoreductase, and TNF-α receptors respectively. SAP-26 has potent interaction -9.8 and -11.0 kcal/mol against EGFR and COX-2 receptors respectively. Whereas, SAP-25 and SAP-19 showed the best interaction for bacterial DNA gyrase (-8.9 kcal/mol) and COX-1 receptor (-9.7 kcal/mol) respectively. To enhance the acceptability top docked compounds, the ADME parameters along with toxicity analysis were carried out where all the compounds showed acceptable results. Furthermore, the stability of the protein-ligand complexes were determined by a 100 ns MD simulation analysis. The common pharmacophore was generated with the help of the top compounds in the PharmaGist web server.