Synthesis, Anticancer Evaluation and Synergistic Effects with cisplatin of Novel Palladium Complexes: DNA, BSA Interactions and Molecular Docking Study

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Author(s): Nenad Joksimović, Nenad Janković, Jelena Petronijević, Dejan Baskić, Suzana Popovic, Danijela Todorović, Milan Zarić, Olivera Klisurić, Milan Vraneš, Aleksandar Tot, Zorica Bugarčić*.

Journal Name: Medicinal Chemistry

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Abstract:

Background: In order to discover new agents for chemotherapy with improved properties related to existing and bearing in mind the fact that some Pd complexes possess better antitumor activity and exhibit less kidney toxicity comparing to cisplatin, series of novel square-planar palladium(II) complexes [Pd (L)2] (3a-f) with O,O bidentate ligands [L = ethyl 2-hydroxy-alkyl(aryl)-4-oxo-2-butenoate] were synthesized.

Methods: All complexes were characterized by spectral (UV-Vis, IR, NMR, ESI-MS) and X-ray analysis and examined for their cytotoxic effect on human cancer cell lines HeLa and MDA-MB 231 and normal fibroblasts (MRC-5). Fluorescence spectroscopic method was used for investigations of the interactions between CT-DNA or bovine serum albumin (BSA) and complex 3c. Viscosity measurements and molecular docking study were performed to confirm the mode of interactions between DNA and BSA and complex 3c.

Results: Complexes that showed best results, 3c, 3d, and 3e, were placed under further investigations. Selected complexes induced apoptosis and cell cycle arrest in HeLa and MDA-MB 231 cells. Low concentrations of 3c and 3e showed strong to moderate synergism with low concentrations of cisplatin. The interaction of 3d with cisplatin was antagonistic in all used concentrations, but low IC50 value indicates its’ usefulness as a single cytotoxic agent. It was also noted that the change of viscosity is more pronounced in DNA solution after addition of complex 3c.

Conclusion: Obtained results indicate that the novel palladium(II) complexes have the potential to become candidates for treatment in anticancer therapy.

Keywords: palladium complexes, antitumor activity, biological activity, DNA binding study, BSA binding study, molecular docking

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Article Details

(E-pub Ahead of Print)
DOI: 10.2174/1573406415666190128095732
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