Synthesis, crystal structure, DFT calculation, Hirshfeld suface analysis and antitumor activity of 4-(tert-butyl)-5-(1H-1,2,4-triazole-1-yl)thiazole derivatives containing benzoxazinone

Seven novel 4-(tert-butyl)-5-(1H-1,2,4-triazole-1-yl)thiazole derivatives containing benzoxazinone (B1-B7) were obtained by cyclization of 4-(tert-butyl)-5-(1H-1,2,4-triazol-1-yl)-N-(2-hydroxy-benzyl)thiazol-2-amine. The chemical structures of the target compounds were confirmed by 1H NMR and 13C NMR. The single crystal X-ray diffraction revealed that B1 crystallizes in a triclinic system with the space group P1. Hirshfeld surfaces and two dimensional (2D) fingerprint plots were employed to quantitatively characterize the influence of intermolecular interactions within the crystal lattice of B1. And the molecular electrostatic potential (MEP) surface was calculated employing Becke-3-Lee Yang Parr (B3LYP)/6-311++G (d,p) theoretical approach. Meanwhile, the Frontier-molecular orbitals of B1 and B2 were calculated using density functional theory (DFT) B3LYP technique with the def2-SVP basis set in the ground state. Preliminary biological tests revealed that the title compounds had certain antitumor activities against three cell lines MCF-7, Hela and A549, and compound B2 presented the most potent antitumor efficacy against A549.