Instigating the In Vitro Anticancer Activity of New Pyridine–Thiazole-Based Co(III), Mn(II), and Ni(II) Complexes: Synthesis, Structure, DFT, Docking, and MD Simulation Studies

The perchlorate salt of (4-(4-methoxy phenyl)-2-(2-(1-pyridine-2-yl)­ethylidene)­hydrazinyl)­thiazole (PytH·ClO 4 ) and its metal perchlorate derivatives, namely, [Co­(Pyt)2]­ClO4 (1), [Mn­(PytH)2]­(ClO4)2 (2), and [Ni­(PytH)2]­(ClO4)2 (3), have been synthesized and characterized through single X-ray crystallography and spectroscopic methods. The ligand crystallizes in a space group P21/n in a nearly planar structure. The overall geometry of the complex salts is described as a distorted octahedron with a MN6 chromophore. The ligand (PytH·ClO 4 ) behaves as a neutral N,N,N-tridentate donor toward the “soft” Mn­(II) and Ni­(II) centers, whereas the deprotonated ligand stabilizes the “hard” Co­(III) center. The DNA binding constant (K b) values of PytH·ClO 4 , 1, 2, and 3 are determined using the UV–vis spectroscopic method, and the K b values are 9.29 × 105, 7.11 × 105, 8.71 × 105, and 7.82 × 105 mol–1, respectively, indicating the intercalative mode of interactions with CT-DNA. All the derivatives show effective antiproliferative activity against U-937 human monocytic tumor cells with IC50 values 4.374 ± 0.02, 5.583 ± 0.12, 0.3976 ± 0.05, and 11.63 ± 0.01 μM for PytH·ClO 4 , 1, 2, and 3, respectively. The best apoptosis mode of cell death is shown by 2 followed by PytH·ClO 4 and 1 at an equivalent concentration of IC50 values. The combined molecular docking and dynamics simulation study evaluates the binding energies of anticancer agents, providing groove binding property with DNA. The 20 ns molecular dynamics simulation study reveals the maximum DNA binding stability of 2 corroborating the experimental results. The new class of metal derivatives of pyridine-thiazole can be used for advanced cancer therapeutics.