Synthesis Characterisation and Biological Evaluation of Schiff Bases Derived from Hydroxy Substituted Benzaldehydes

Abstract

Literature survey inferred that the maximum number of antibiotics have amine group as one of the functional groups because of its good binding nature. However, it causes side effects in human beings. Hence it is proposed to protect the amine group of the selected pharmacores by condensing it with substituted benzaldehydes. To identify the active functional group for better biological activities, this research selected the secondary amide functional group, thiazole group and chiral group from the reference drug molecules. Nineteen Schiff bases were synthesized from the selected functional groups and all were characterized thoroughly by various spectral techniques such as UV visible, Fluorescence, FT-IR, 1H-NMR, 13C-NMR and Mass spectra. The quantitative structure-activity relationship (QSAR) of the Schiff bases were computed using online Molsoft and offline Spartan-14 wave function Density functional theory (DFT) software and correlated with Lipinski five drug-likeness rules. In addition to the QSAR evaluation, hard and soft nature of the molecules were determined from the energy gap between Highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) using Gaussian09 DFT software. Docking affinity of the Schiff bases against the protein targets such as PDB ID: 1SHV (E.coli), PDB ID: 1A2N (E.coli biofilm), PDB ID: 1HSK (Staphylococcus aureus biofilm), PDB ID: 1S1J (Zipa cell division), PDB ID: 1XCW (and#945; Amylase), PDB ID: 3K0K (Breast cancer type 1 susceptibility protein) and PDB ID: 3FDN (Aurora A kinase) were also evaluated. From the protein-ligand interactions, docking score was calculated for all the Schiff bases. The docking study was carried out using mcule 1-click docking online server and the high score poses were imported and verified by CLC drug discovery workbench-3 software. From the outcomes of the computational study, the toxicity of the Schiff bases was assayed by brine shrimp lethal assay at controlled conditions for the in-vivo concentration limit purpose and LC50 were d