Discovery of a novel oxadiazine derivative of glucocorticoids endowed with DNA binding activities and molecular docking studies

A series of new glucocorticoid oxadiazines (4–6) were synthesized by reacting glucocorticoids (1–3) with thiosemicarbazide and its derivatives. The structural assignment of products is confirmed on the basis of IR, 1H NMR, 13C NMR, MS and analytical data. The synthesized compounds (4–6) obeyed the Lipinski’s “Rule of Five” analysis based on a computational prediction of molecular and pharmacokinetic properties. The interaction studies of compounds (4–6) with DNA were carried out by employing single-cell gel electrophoresis (comet assay), UV-vis and fluorescence spectroscopy. Compounds (4–6) were found capable of cellular DNA degradation breakage in isolated normal human lymphocytes. Viscometric and steady-state measurements further correlated with the comet assay studies. Hence, it could be suggested that the glucocorticoid compounds bearing a core oxadiazine scaffold would be a potent biological agent. Molecular docking studies further characterize the interaction of the synthesized compounds with DNA. GRAPHICAL ABSTRAC