Synthesis, characterization, DFT analysis and docking studies of a novel Schiff base using 5-bromo salicylaldehyde and β-alanine

Poly(ADP-ribose) polymerase-1(PARP-1) is a DNA-dependent enzyme, forming part of ADP-ribosyltransferase family. Although some PARP inhibitors find therapeutical applications in cancer therapy and exhibits crucial role in DNA damage response. Here a novel Schiff base, (E)-3-((5-bromo-2-hydroxybenzylidene) amino) propanoic acid was synthesized using 5-bromo salicylaldehyde and β-alanine. Characterization was carried out using IR, UV-Vis,(1)H and (13)C NMR and mass spectrum. Present study involves the evaluation of a novel Schiff base as an inhibitor against human breast cancer cell lines (pdb:3GEY) using 2-(dimethylamino)-N-(6-oxo-5,6-dihydrophenanthridin-2-yl) acetamide (DDA) as a native ligand. In silico study of 3GEY inhibitor is a variant of PARP-15, docking with two different ligands (E)-3-((5-bromo-2-hydroxybenzylidene) amino) propanoic acid (SBL) and the native ligand. Synthesized ligandis docked in to the B chain of PARP enzyme binding site to visualize the best docked poseand favorable ligand-protein binding interactions. Swiss ADME tool determines the drug likeness and strongly suggests that SBL can be a promising candidate to fight against breast cancer. DFT studies were done to support the experimental results using B3LYP/6-311+G(d,p) and geometry optimization was performed. Various thermodynamic parameters and NLO properties were found out. ECD and VCD spectrum were explained using DFT studies. Vibrational and Raman frequencies were also reported. HOMO-LUMO band gaps, Mulliken charges were calculated and the electrostatic potential surface was mapped with various properties. Experimental findings obtained are in good agreement with that of theoretical DFT analysis.