Structural elucidation, Hirshfeld surface, DFT, molecular docking and molecular dynamics studies of a novel thiazole derivative as anti-cancer drug

Detailed structural and non-covalent interactions in the novel thiazole derivative benzyl 4-(4-chlorophenyl)thiazole-2-carboxylate (6a) has been synthesized and characterized by spectroscopic characterizations like ¹H NMR and ¹³C NMR, and single crystal structure analysis. Its results were compared with the previously reported similar thiazole derivative (4-methoxyphenyl)methyl 4-(4-chlorophenyl)-1,3-thiazole-2-carboxylate (6b). The crystal structure analysis revealed that C–H……O, hydrogen bonds involved in stabilizing the crystal packing. The differences and similarities in the relative contribution of non-covalent interactions in 6a and 6b compounds are compared using the Hirshfeld surface analysis and 2D fingerprint plots. The binding energies of specific molecular pairs and dimers have been investigated using pair-wise interaction energy calculation. The hierarchy and supramolecular architecture of intermolecular interactions are visualized through energy frameworks. Geometric parameters of the optimized structure were determined using DFT calculations on the B3LYP/6–311++G(d,p) basis set and compared to X-ray diffraction data. Molecular docking with the 6FS1 protein revealed a binding score of 6a is -6.7 kcal/mol, and 6b is -6.5kcal/mol indicating potential anticancer action for the thiazole compound. Furthermore, the binding interaction was investigated using dynamics modelling simulations. Further in vitro and in vivo analysis will help in the exploration of the inhibition activity of the ligand with the protein.