Rational Design of Threo as Well Erythro Noscapines, an Anticancer Drug: A Molecular Docking and Molecular Dynamic Approach

Noscapine (narcotine) is an opium alkaloid, isolated from Papaver somniferum L. Noscapine is being used in clinical trials for curing cancer. Till date researchers mainly discussed the erythro form of noscapine but in the present work the authors have discussed the erythro as well as threo form of noscapine. In the present work, library of 11 derivatives of noscapine from each of threo- and erythro- isomer was created and virtually screened for their chemotherapeutic efficacy on Tyrosine Kinase Domain from Epidermal Growth Factor Receptor (PDB-1M14). The interaction between Tyrosine Kinase Domain of Epidermal Growth Factor Receptor and noscapines was studied by means of docking based on lowest binding energy and top pharma score and Molecular Dynamic (MD) simulation. It was found erythro form aminonoscapine (13) have higher binding affinity against the Tyrosine Kinase Domain and further, MD simulation was performed. Compound 13 showed acceptable hydrophobicity and solubility value. Further, threo form of nitronoscapine (11) also showed good interaction based on docking, simulation and comes out to be acceptable like a drug based on hydrophobicity and solubility value.