Synthesis, crystal structure, Hirshfeld surface analysis, DFT, molecular docking and in vitro antitumor studies of (2E)-2-[4-(diethylamino)benzylidene]-N-ethylhydrazinecarbothioamide

Abstract

The crystal structure and spectral characterization of a new proligand, (2E)-2-[4-(diethylamino)benzylidene]-N-ethylhydrazinecarbothioamide is described. The compound was crystallized in the monoclinic space group P21/c; Z = 8, V = 3192.7(8) Å3 with unit cell parameters a = 26.232(4) Å, b = 7.9196(10) Å, c = 15.369(3) Å,α = 90°, β = 90.217(6)° and γ = 90°. There are two independent molecules in the asymmetric unit. The crystal structure reveals that the compound exists in the thione form and S1 and N2 are at E configuration to each other with respect to N3–C12 bond. Similarly, S2 and N6 are trans to each other with respect to N7–C26 bond in the second molecule of the asymmetric unit. The packing of the molecules in the crystal lattice is stabilized by intermolecular hydrogen bonds, which are quantified with Hirshfeld surface analysis. The synthesized compound was characterized by IR, UV–vis, 1H and 13C NMR spectra. DFT study indicates the molecular chemical stability with a HOMO-LUMO energy gap of 3.79 eV. The molecule is soft with preference for NS coordination mode. The azomethine nitrogen and thione sulfur region are electron rich and can act as a nucleophilic site to bind with the electrophilic regions of DNA or protein receptors. The in silico docking study with 1BNA suggests that the compound can fit comfortably in the curved shape of the DNA target like a minor groove mode of binding. The in vitro cytotoxicity of the compound, which was screened for DLA tumour cells aspirated from the peritoneal cavity of tumor bearing mice, is indicative of its antitumor potential.