Synthesis, X-ray, spectroscopic characterization (NMR, FT-IR, Raman, and UV-VIS), Hirshfeld surface analysis, DFT, molecular docking, and estimating anticancer of 5,6-diphenyl-3-(prop-2-yn-1-ylthio)-1,2,4-triazine

A new 1,2,4-triazine derivative, 5,6-diphenyl-3-(prop-2-yn-1-ylthio)-1,2,4-triazine (4) has been synthesized through the condensation of 5,6-diphenyl-1,2,4-triazine-3-thiol with propargyl bromide in acetone solution in the presence of triethylamine at room temperature for one hour. Its chemical structure was elucidated from spectral data (1H NMR, 13C NMR, FT-IR, FT-Raman, UV/Vis, and mass spectrometry) and confirmed by a single crystal X-ray diffraction analysis. Geometrical optimization of the molecular structure was performed at the B3LYP/6-311++G(d,p) level of theory. The intercontacts between different units in the crystal of 4 were explored by a Hirshfeld surface analysis (HSA), which reveals that H...H contact has the highest contribution of intermolecular contacts. The anticancer activity of 4 was explored by estimating its binding affinity into the binding site of human DNA topoisomerase as the molecular target of various anticancer compounds using molecular docking. This study indicated 4 to fit well into the DNA topoisomerase binding site and to form a stable complex with its amino acids. The ADMET properties reveal that 4 obeys Lipinski's rule of five, has high gastrointestinal (GI) absorption, and may exhibit penetration through the Blood-Brain Barrier (BBB).