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

• DOI: 10.1021/acs.jcim.1c01280
• Publication Date: 2022-03-07T11:40:32Z
• Authors: Pradip Bera; Abhishek Aher; Paula Brandao; Utsab Debnath; Varun Dewaker; Sunil Kr. Manna; Abhimanyu Jana; Chandana Pramanik; Basudev Mandal; Pulakesh Bera
• Keywords: Thiazole; Perchlorate; Octahedral molecular geometry; Docking (animal)

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