Computational identification of bioactive compounds from Cydonia oblonga Mill. against hepatocellular carcinoma by targeting pTEN and HBx-interacting protein.

Phytochemicals derived from Cydonia oblonga have been investigated for their anti-oxidant and anti-cancer activities in various cancer cell lines. The reported bioactive compounds are evaluated in silico to develop a novel antagonist against pTEN (phosphatase and tensin homolog) and HBx (hepatitis B X-interacting protein) to target hepatocellular carcinoma. Lower expression of pTEN or higher expression of HBx represents the progression of hepatocellular carcinoma. This research is intended to identify the best candidate who interacts with our target proteins (pTEN and HBx) from the quince seeds by using computational methodologies. The ternary structures of the proteins and phytochemicals are retrieved from the online databases (RCSB and PubChem). The drug likeness analysis of the reported seventeen compounds was done, but only five follow the selection criteria. ADMET profiling of these five compounds was done, followed by docking analysis and molecular dynamics study of the best complexes to determine the stability of the complexes. A docking study revealed that caffeoylquinic acids (CQA) derivatives have the significant inhibitory potential of 3-O-caffeoylquinic acid (3CQA) and 5-O-caffeoylquinic acid (5CQA) with binding affinity of - 7.53 and - 7.49 against pTEN and - 5.94 and - 6.01 against HBx in comparison to the doxorubicin. The average root mean square deviation and root mean square fluctuation values for protein-ligand complexes were found quite stable compared to the standard, while parameters like gyration and SASA (solvent-accessible surface area) supported the complexes significant binding and stability. The results obtained from the evaluation show that 3CQA and 5CQA have the best stability, especially with the pTEN protein target. Hence, these compounds have to be considered for detailed experimental studies to understand their biological function against hepato-carcinoma.