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Synthesis, Characterization and Biological Studies of Organoselenium trans-Palladium(II) Complexes

Author(s):

Ivana Raković, Jovana Bogojeski*, Katarina Mladenović, Angelina Petrović, Vera Divac, Kristina Mihailović, Biljana Popovska Jovicić, Marina Kostić, Predrag Canović, Nevena Milivojević, Marko Zivanović and Ivana Radojević   Pages 1 - 16 ( 16 )

Abstract:


Background: Over the years, transition metal complexes have exhibited significant antimicrobial and antitumor activity. It all started with cisplatin discovery, but due to the large number of side effects it shows, there is a growing need to find a new metal-based compound with higher selectivity and activity on more tumors.

Objectives: Two novel trans-palladium(II) complexes with organoselenium compounds as ligands, [Pd(L1)2Cl2] (L1 = 5- (phenylselanylmethyl)-dihydrofuran-2(3H)-one) and [Pd(L2)2Cl2] (L2 = 2-methyl-5-(phenylselanylmethyl)- tetrahydrofuran) were synthesized, in the text referred to as Pd-Se1 and Pd-Se2. Also, a structurally similar trans-palladium(II) complex, [Pd(L3)2Cl2] (L3= 2,2-dimethyl-3-(phenylselanylmethyl)-tetrahydro-2H-pyran ) was synthesized according to an already published work and is referred to as Pd-Se3. The interaction of synthesized complexes with DNA and bovine serum albumin were done. Also, antimicrobial activity and in vitro testing, cell viability, and cytotoxic effects of synthesized ligands and complexes on human epithelial colorectal cancer cell line HCT-116 were studied. Molecular docking simulations were performed to understand better the binding modes of the complexes reported in this paper with DNA and BSA, as well as to comprehend their antimicrobial activity.

Methods: The interactions of the synthesized complexes with DNA and bovine serum albumin were done using UV-Vis and emission spectral studies as well as docking studies. Antimicrobial activity was tested by determining the minimum inhibitory concentrations (MIC) and minimum microbicidal concentration (MMC) using the resazurin microdilution plate method. Cytotoxic activity on cancer cells was studied by MTT test.

Results: The Pd(II) complexes showed a significant binding affinity for calf thymus DNA and bovine serum albumin by UV-Vis and emission spectral studies. The intensity of antimicrobial activity varied with the complexes Pd-Se1 and Pd-Se3, showing significantly higher activity than the corresponding ligand. The most significant activity was shown on Pseudomo-nas aeruginosa. Under standardized laboratory conditions for in vitro testing, cell viability and cytotoxic effects of synthesized ligands and complexes were studied on human epithelial colorectal cancer cell line HCT-116, where Pd-Se2 showed some significant cytotoxic effects.

Conclusion: The newly synthesized complexes have the potential to be further investigated as metallodrugs.

Keywords:

Palladium, Selenium, DNA, Docking, Antimicrobial activity, Cytotoxicity.

Affiliation:

University of Kragujevac, Faculty of Medical Sciences, Svetozara Markovića 69, Kragujevac, 34000, University of Kragujevac, Faculty of Science, Radoja Domanovica 12, Kragujevac, 34000, University of Kragujevac, Faculty of Science, Radoja Domanovica 12, Kragujevac, 34000, University of Kragujevac, Faculty of Science, Radoja Domanovica 12, Kragujevac, 34000, University of Kragujevac, Faculty of Science, Radoja Domanovica 12, Kragujevac, 34000, University of Kragujevac, Faculty of Science, Radoja Domanovica 12, Kragujevac, 34000, University of Kragujevac, Faculty of Medical Sciences, Svetozara Markovića 69, Kragujevac, 34000, University of Kragujevac, Institute for Information Techonlogies, Jovana Cvijića bb, Kragujevac, 34000, University of Kragujevac, Faculty of Medical Sciences, Svetozara Markovića 69, Kragujevac, 34000, Laboratory for Bioengineering, BioIRC - Bioengineering Research and Development Center, Prvoslava Stojanovića 6, Kragujevac, 34000, Laboratory for Bioengineering, BioIRC - Bioengineering Research and Development Center, Prvoslava Stojanovića 6, Kragujevac, 34000, University of Kragujevac, Faculty of Science, Radoja Domanovica 12, Kragujevac, 34000



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