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

Article abstract of DOI:10.1016/j.inoche.2021.108846

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 (L¹ and L²) 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, L¹-Pd and L²-Pd were found to display significant cytotoxicity with IC₅₀ values of 10.21 μM and 10.79 μM 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 L¹-Pd and L²-Pd induced apoptosis and a slight decrease in anti-apoptotic Bcl-2 protein/gene expression and highly increased pro-apoptotic Bax protein/gene expression in MKN-45 cells treated. Also, total DNMT enzyme activity and protein expression (DNMT1, DNMT3a, and DNMT3b) levels were decreased in L¹-Pd and L²-Pd treated cells. The L¹-Pd and L²-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.