In silico analysis of hexokinase- I and II as potential drug targets in cancer

Objective: Hexokinases in the glycolytic pathway exhibit enhanced catalytic activity in malignant cells. In order to control cancer cell growth, the activity of the enzyme needs to be dampened. In the present study, an in silico approach is made to find potential phytochemical inhibitors of hexokinase I and II.Methods: ArgusLab software is used to study the binding affinity of ligands in the active site of the protein. Computation of drug-likeness and oral toxicity is done using the online tools Molsoft and ProTox respectively.Results: A flavonoid, 1, 2-dihydrobis (de-O-methyl)-curcumin, shows better binding affinity to the substrate as well as cofactor binding sites of both hexokinase I and II. The LD50 value (median lethal dose) is 2000 and the toxicity class is 4. There is no tox related fragments found in this structure and no possible binding to any toxicity targets.Conclusions: 1, 2-dihydrobis (de-O-methyl)-curcumin is the inhibitor of choice, a lead molecule against targets: hexokinase I and II. The lead molecule may be the future drug for cancer treatment.