ANTICANCER POTENTIAL OF NOVEL PALLADIUM(II) COMPLEXES WITH ACYL PYRUVATES AS LIGANDS: DNA AND BSA INTERACTIONS AND MOLECULAR DOCKING STUDY

Bearing in mind that some palladium complexes showed good antitumor potential while exhibiting less kidney toxicity comparing to cisplatin, to discover a new agents for chemotherapy with improved properties two novel palladium(II) complexes [Pd (L)2] (3A and 3B) with acyl pyruvates (O,O bidentate ligands) were synthesized and characterized by spectral (UV-Vis, IR, NMR, ESI-MS) and elemental analysis. The novel palladium(II) complexes were analyzed for their cytotoxic potential on human cancer cell lines (HeLa and MDA-MB 231) and normal fibroblasts (MRC-5). Results showed that complex 3A displayed very good cytotoxic activity, while complex 3B had moderate activity on the tested tumor cell lines. After 48h incubation with complex 3A, his IC50 values were similar to the IC50 values of cisPt. Notably, all IC50 of complex 3A on human fetal lung fibroblasts (MRC-5) were higher than 100 μM, indicating good selectivity. In addition, complex 3A induced apoptotic type of cell death, cell cycle arrest in G0/G1 phase in both HeLa and MDA-MB 231 cell lines. In addition, we revealed that 3A can be useful as adjuvants in cancer therapy by reducing the dose of cisplatin and in this manner its’ side effects. For the investigations of interactions between novel palladium(II) complex 3A and CT-DNA or bovine serum albumin (BSA) fluorometric titrations method was used. The obtained results implied that 3A has great affinity to displace ethidium bromide (EB) from the EB-DNA complex through intercalation, suggesting strong competition with EB. Results in fluorescence titration of BSA with complex 3A showed that the fluorescence quenching of BSA happens because of the formation of the 3A-BSA complex. Obtained Ka value is in the optimal range signifying that appropriate amount of 3A can be transported and distributed through the cells. In order to better understand the binding of newly synthesized complex 3A to BSA or DNA, molecular docking study was further performed.