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

Area of Science:

• Medicinal Chemistry
• Inorganic Chemistry
• Cancer Biology

Background:

• Piperidine scaffolds are prevalent in biologically active molecules.
• Hydrazone derivatives and their metal complexes are explored for therapeutic applications.
• Platinum and palladium complexes are established anticancer agents.

Purpose of the Study:

• To synthesize and characterize novel piperidine-based hydrazone ligands and their Pt(II) and Pd(II) complexes.
• To evaluate the in vitro anticancer activity of these compounds against lung (A549) and liver (HepG2) cancer cell lines.
• To investigate the molecular mechanisms underlying their anticancer effects.

Main Methods:

• Synthesis of piperidine-based hydrazones via condensation reactions.
• Complexation of ligands with K₂PtCl₄ and K₂PdCl₄ to form Pt(II) and Pd(II) complexes.
• Structural elucidation using spectral methods and elemental analysis.
• In vitro evaluation of cytotoxicity (IC₅₀), wound-healing/migration, and gene expression (RT-qPCR) assays.
• In silico molecular docking studies.

Main Results:

• Compound 3lPd demonstrated potent cytotoxicity against A549 cells (IC₅₀ = 61.25 µM) and significantly inhibited cell migration.
• Ligand 3b and complex 3nPt showed notable effects on HepG2 cells (IC₅₀ = 77.96 and 77.01 µM, respectively).
• 3lPd suppressed MYC and reduced p53 expression in A549 cells, comparable to cisplatin.
• 3nPt decreased p53 in HepG2 cells, while 3b upregulated p53.
• In silico studies explored interactions with key cancer-related proteins (p53, GAPDH, c-MYC).

Conclusions:

• Piperidine-bearing hydrazones and their Pt(II)/Pd(II) complexes are promising anticancer scaffolds.
• Compound 3lPd exhibits significant potential for lung cancer therapy.
• Complex 3nPt and ligand 3b show promise for hepatocellular carcinoma treatment.
• Further investigation into these metal complexes could lead to novel anticancer drug development.