Design, synthesis and investigation of procaine based new Pd complexes as DNA methyltransferase inhibitor on gastric cancer cells

Procaine is a specific inhibitor of DNA methyltransferase (DNMT). In the present work, the Schiff base ligands were synthesized from procaine with the addition of salicylaldehyde and naphthaldehyde as metal precursor for procaine-based transition metal complexes (L-1 and L-2) with palladium (Pd). The compounds were checked and characterized for identity and purity using elemental analysis, SEM, melting points, FT-IR, and NMR spectral data. Among the compounds, L-1-Pd and L-2-Pd were found to display significant cytotoxicity with IC50 values of 10.21 mu M and 10.79 mu M against human gastric cancer cell line MKN-45. Novel synthesized procaine derivatives target molecules and their palladium complexes had an inhibitory effect on colony formation and wound healing on MKN-45 cells. Furthermore, these compounds were evaluated for their apoptotic activity and DNMT activity in MKN-45 cells. Western blotting and qPCR studies demonstrated that compound L-1-Pd and L-2-Pd induced apoptosis and a slight decrease in anti-apoptotic Bcl-2 protein/gene expression and highly increased proapoptotic Box protein/gene expression in MKN-45 cells treated. Also, total DNMT enzyme activity and protein expression (DNMT1, DNMT3a, and DNMT3b) levels were decreased in L-1-Pd and L-2-Pd treated cells. The L-1-Pd and L-2-Pd complexes showed that they are potential new DNMT inhibitors to prevent cancer-induced DNA hypermethylation and can be used in the treatment of gastric cancer.

Automated summary

The procaine derivatives combined with palladium demonstrated significant cytotoxicity against human gastric cancer cells, inhibiting colony formation and wound healing, and inducing apoptosis. Furthermore, these complexes showed potential as new DNMT inhibitors for preventing cancer-induced DNA hypermethylation.