Single crystal XRD, DFT investigations and molecular docking study of 2- ((1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)amino)naphthalene-1,4-dione as a potential anti- cancer lead molecule.

A derivative of naphthaquinone, 2-((1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)amino)naphthalene-1,4-dione (DPDHN) was synthesized from lawsone by ultrasound accelerated technique. The compound was characterized by elemental analysis, IR, UV-vis, NMR and mass spectral studies. Single crystal X-ray diffraction studies revealed that the compound crystallized in monoclinic space group P2₁/c. Density functional calculations of DPDHN was performed using DFT (B3LYP) method with 6-311G (5D, 7F) basis set, geometrical optimization best fit to single crystal XRD values. The charge delocalization has been analyzed using natural orbital (NBO) analysis. Effects of halogenations at ortho, meta and para positions in the title compound is discussed for frontier molecular orbital analysis, molecular electrostatic potential plots and nonlinear optical properties. It exhibited significant antioxidant property. To predict the anticancer activity of the compound, molecular docking studies were done using Schrödinger software. Molecular docking studies for DPDHN was performed on the active site of protein kinase CK2 (PDB ID: 2OXX, 1M2R and 1M2P) and to explore the estrogen receptor binding ability, the target protein with PDB ID: 3ERT and 2YLY were selected. Docking scores of the designed compound was compared with FDA approved drugs, Tamoxifen, Daunorubicin and Doxorubicin. The compound DPDHN exhibited good Glide scores for all the proteins. Glide score of DPDHN (PDB ID: 2YLY) was -9.67 kcal/mol which was as good as the currently used breast cancer drug, Tamoxifen (-10.37 kcal/mol) and found better than the drug Doxorubicin (-7.3 kcal/mol). Lead compound that satisfies predefined minimum criteria further structure and activity optimization. In the present work, hence it was further subjected to in vitro studies towards human breast cancer (MCF-7) and colon cancer (HCT-15) cell lines. The IC₅₀ value of compound DPDHN in MCF-7 cells was 15.21 μM and that of HCT-15 was 39.21 μM which was a lower value and better than that of lawsone. Therefore DPDHN exhibited much higher toxicity towards MCF-7 cell lines. Thus, the results indicate that DPDHN is a potential anti cancer lead molecule especially for breast cancer studies.