Spectroscopic, docking, antiproliferative, and anticancer activity of novel metal derivatives of phenylacetohydrazide Schiff base on different human cancer cell lines

In the last two decades, many Schiff bases have been investigated due to the importance of their metal complexes in the medical field and drug industry. The Schiff base metal complexes have several applications as anticancer agents because they have a high binding ability to nucleic acids (DNA and RNA). The Schiff base H₂L, derived from the condensation of 2-phenylacetohydrazide and 2-hydroxynaphthaldehyde, was reacted with Fe²⁺, Zn²⁺, Cd²⁺, and Pt²⁺ to form the unique metal complexes [Fe(HL)₂], [Zn₂(HL)₂](CH₃COO)₂, [Cd₂(HL)₂](CH₃COO)₂, and [Pt(H₂L)Cl₂]. Various analytical and spectroscopic techniques were used to characterize the newly reported compounds. The elemental and spectroscopic analysis revealed that the platinum complex was a square planar with 2.5 water molecules in the crystal lattice, whereas the iron complex had an octahedral geometry. The thermogravimetric analysis demonstrated the stability of the complexes and validated the dimerization of zinc and cadmium complexes. DFT calculations were investigated to obtain the optimized structure of the ligand and its complexes. Biological screening and molecular docking studies of the ligand and complexes were reported to explore their potential application as therapeutic drugs. Among the tested complexes, [Cd₂(HL)₂](CH₃COO)₂ complex showed the best cytotoxic effect, especially on the human colorectal cancer cell line (HCT116, IC₅₀ = 0.329 µg/ml) as compared to normal human skin fibroblast (HSF, IC₅₀ = 5.240 µg/ml) and selectivity index (SI) = 15.93. It represents a promising anticancer drug compared to Cisplatin (IC₅₀ = 2.25µg/ml, SI = 4.92). The biological studies and molecular docking were correlated to each other.