The Discovery and Development of New Liver Cancer Stem Cell Inhibitor: Exploitation of Molecular Modeling: QSAR Modeling, ADMETox, Molecular Docking, Biological Efficacity and Retrosynthesis

This study examined the possibility of using innovative isoxazole derivatives as agents for treating liver cancer, combining several computational methods. A reliable model (QSAR) was used to identify six compounds (Pr1-Pr6) with high anticancer activity compared to that of the anticancer drug SORAFENIB (SOR). The Lipinski characteristics and synthetic accessibility coefficient of the newly developed compounds suggest their potential for therapeutic use. Candidate Pr3 has a stronger binding affinity with the target receptors (PDB ID: 1QX3 and 2AR9) compared to the other compounds. The study of the transport of candidates through the tunnels linking the active site and the receptor surface allows their biological efficiencies to be compared. Computer-aided retrosynthesis enabled us to propose highly reliable sequences for the synthesis of the proposed drug candidates. The results provide valuable information on the potential use of these compounds for the treatment of liver cancer.