Hepatocellular carcinoma (HCC) is a major public health problem and the leading cause of death of people around the world with a tendency to increase every year, leading to a large investigation on the development of HCC drugs. In this work, novel sorafenib derivatives containing 1,2,3-triazole moiety, M1-M5 were designed as potential HCC cancer inhibitors by targeting B-rapidly accelerated fibrosarcoma (B-RAF) and vascular endothelial growth factor receptor 2 (VEGFR-2). The bindings of M1-M5 in the cavity of B-RAF and VEGFR-2, which are kinases related to HCC cell growth, were investigated by molecular docking using iGEMDOCK v2.1 software. The results illustrated that M1-M5 bound in the binding site of B-RAF and VEGFR-2 in a similar manner to sorafenib. It was also found that the 1,2,3-triazole moiety of M1-M5 interacted well by hydrogen bonding with key amino acids in the binding site of B-RAF and VEGFR-2 which could inhibit the cancer cell growth. Although the binding energies of M1-M5 in B-RAF (-148.51 to -126.19 kcal/mol) were rather higher to that of sorafenib (-176.75 kcal/mol), the binding energies of M1-M5 in VEGFR-2 (-127.00 to -116.48 kcal/mol) were comparable to that of sorafenib (-127.03 kcal/mol). As a result, M1-M5 containing 1,2,3-triazole moiety were promising molecules to study in vitro on VEGFR-2 inhibitory assay and be leading compounds for the development as the anticancer drugs against HCC in the future.

Cancer is currently a major public health concern worldwide. Previous studies have shown that heat shock protein 90 (Hsp90) is the key common cause of cancer. Thus, Hsp90 is one of the important molecular targets for the development of Hsp90 cancer drug based on geldanamycin (GDM) and alvespimycin (17-DMAG). Herein, novel geldanamycin derivatives, S1-S6 were designed as potential Hsp90 cancer drug by targeting signal transduction pathway, especially against oncogenic client protein from Hsp90. The binding of S1-S6 in the cavity of Hsp90 were investigated by molecular docking using the iGEMDOCK v2.1 software. The results illustrated that S1-S6 bound in the binding site of Hsp90 with similar manner to GDM and 17-DMAG. The binding energies of S1-S6 in Hsp90 (PDB ID:1YET) (-137.49 to -123.24 kcal/mol) were comparable to that of GDM (-133.06 kcal/mol) while the binding energies of S1-S6 in Hsp90 (PDB ID:1OSF) (-137.49 to -131.22 kcal/mol) were slightly higher than that of 17-DMAG (-145.31 kcal/mol). S1-S6 interacted well by hydrogen bonding with key amino acids in the binding site of Hsp90, which could inhibit the cancer cell growth. Therefore, S1-S6 containing novel geldanamycin derivatives could be promising molecules for anti-cancer drug against Hsp90 2 types in the future.