Unveiling the potential of bioactive compounds from Linum usitatissimum L. to target Hepatocellular carcinoma: an in silico based approach

Bioactive metabolites from Linum usitatissimum L. have been extensively explored for their anti-cancer and antioxidant potential in several cancer cell lines. The bioactive chemicals that have been reported are being assessed using in silico methods to create a new antagonist that may effectively target hepatocellular carcinoma by inhibiting c-Kit (stem cell factor receptor) and HBXIP (hepatitis B X-interacting protein). Dysregulation in function or overexpression of c-Kit and HBXIP shows the development of hepatocellular carcinoma. The objective of this study is to use computational approaches to choose the most suitable candidate that interacts with our chosen target proteins, c-Kit and HBXIP, derived from flaxseed. From the online resources, namely RCSB and PubChem, the 3D structures of the proteins and bioactive compounds are obtained. The drug likeness study and ADMET profiling of these bioactive compounds were performed, and the selected fourteen compounds were considered for docking analysis. The molecular docking study revealed that secoisolariciresinol (SECO) has a comparable interaction affinity of -5.5 kcal/mol and -7.5 kcal/mol with HBXIP and c-KIT, respectively, when compared to the redock co-crystal complex (-3.5 kcal/mol and -12.4 kcal/mol, respectively). The results of the molecular dynamics simulation study demonstrate the constancy of the SECO_HBXIP and SECO_c-Kit complexes when compared to the redock complex. The average root-mean-square fluctuation (RMSF), root-mean-square deviation (RMSD) values, gyration (Rg) and hydrogen bonding provide additional evidence of the significant binding and stability of the complexes. Moreover, in vitro cell viability assay on HepG2 also showed a significant reduction in the cell proliferation after the treatment with SECO.