In silico analysis of isoquinoline alkaloids using Cathepsin L as target receptor for controlling metastasis

Metastasis had been a challenging concern for the oncologists in the progressive state of cancer. ubiquitous lysosomal cysteine proteinase, cathepsin L which plays an important role in metastasis in a variety of cancer cells has been taken as a target enzyme. Exploration of natural isoquinoline alkaloids as versatile biological agents is a keen research interest for the medicinal chemists. We have made an effort to screen phytochemical inhibitor virtual by molecular docking and dynamic simulation in the current research. For binding affinity evaluation of all 10 isoquinoline alkaloids, the docking scores and non-covalent interactions and dihedral angles were calculated using Autodock Vina. It suggested that two isoquinoline alkaloids, Isoliensinine and Dauricine were found to be promising binding agents, with binding energy values − 9.6 kcal/mol and − 9.1 kcal/mol, respectively. The inhibitory action of the phytocompounds was also validated by comparing with standard cathepsin L inhibitor Olegatrelvir. These probable potent isoquinoline alkaloids as were subjected to the calculation of physicochemical properties and prediction of analysis of ADME parameters using Swiss ADME platform. Further, molecular dynamic studies resulted in the excellent RMSD values and satisfactory conformational ability. These results will help to design derivatives based on Isoliensinine and Dauricine as potent cathepsin L inhibitors.