Piperidine-Based Hydrazones and Their Pt(II)/Pd(II) Complexes: Synthesis, Structural Characterization, In Vitro...

In this study, 2-(4-methylpiperidin-1-yl)acetohydrazide was condensed with a series of substituted benzaldehydes to afford a library of piperidine-based hydrazones, which were subsequently complexed with K₂PtCl₄ and K₂PdCl₄ to yield the corresponding Pt(II) and Pd(II) complexes. The structures of molecules were elucidated by spectral methods and elemental analysis. The in vitro anticancer potential of the compounds was evaluated through cytotoxicity, wound-healing/migration, and RT-qPCR assays in A549 (lung) and HepG2 (hepatocellular) cancer cell lines. In the cytotoxicity studies, compound 3lPd exhibited the highest activity in A549 cells (IC₅₀ = 61.25 ± 0.03 µM), while ligand 3b and complex 3nPt showed the most pronounced effects in HepG2 cells (IC₅₀ = 77.96 ± 0.05 and 77.01 ± 0.02 µM, respectively). The most active compounds were further tested in wound-healing assays, where 3lPd almost completely inhibited A549 cell migration at 24 and 48 h, whereas the reference drug cisplatin induced only partial inhibition. Consistent with these findings, RT-qPCR analysis revealed that in A549 cells, 3lPd markedly suppressed MYC expression and reduced p53 levels to an extent comparable to cisplatin. In HepG2 cells, 3nPt decreased p53 expression, while L3b uniquely upregulated p53 and maintained MYC expression near control levels. In silico studies were performed to investigate their interactions with p53, GAPDH, and c-MYC proteins. Overall, these results suggest that piperidine-bearing hydrazones and their Pt(II)/Pd(II) complexes represent promising scaffolds for the development of novel anticancer agents.