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The four new ligands, propylenediamine derivatives of phenylalanine (R 2 - S , S -pddbaˑ2HCl; L1 - L4) and their palladium(II) complexes (C1 - C4) were synthesized and characterized by elemental analysis, infrared, 1H and 13C NMR spectroscopy. The interactions of new palladium(II) complexes with human serum albumin (HSA) were studied by fluorescence spectroscopy. All investigated compounds can be transported to target cells by binding to HSA, but complex C4 interacts most strongly. Molecular docking simulations were applied to comprehend the binding of the complex to the molecular target of HSA. Obtained results are in good correlations with experimental data regarding binding affinity by HSA. In vitro cytotoxicity activities were investigated on four tumor cell lines (mouse mammary (4 T1) and colon (CT26), human mammary (MDA-MD-468) and colon (HCT116)) and mouse mesenchymal stem cells as non-tumor control cells. Cytotoxic capacity was determined by MTT test and according to obtained results ligand L4 stands out as the most active and selective compound and as a good candidate for future in vivo testing. Further examination of the ligand L4 and corresponding complex C4 led to the conclusion that both induced cell death mainly by apoptosis. Ligand L4 facilitated cycle arrest in G0/G1 phase and decreased proliferative capacity of tumor cells. In vitro antimicrobial activity for ligands and corresponding Pd(II) complexes was investigated against eleven microorganisms (eight strains of pathogenic bacteria and three yeast species) using microdilution method. The minimum inhibitory concentration and minimum microbicidal concentration were determined. The four new ligand and their pallladium(II) complexes were synthesized and characterized by elemental microanalysis, IR, 1H, 13C NMR spectroscopy. The interactions of complexes with HSA were determined and molecular doking simulation were performed. In vitro cytotoxic and antimicrobial activity were tested. [Display omitted] • Four new ligand were synthesized by new method. • Four new palladium(II) complexes were synthesized. • Characterization was performed by IR, 1H and 13C NMR spectroscopy. • The interactions of complexes and molecular docking with HSA were investigated. • Cytotoxic and antimicrobial activities of all compaunds were evaluated. [ABSTRACT FROM AUTHOR]

Newly palladium(II) complexes (C1 , C2) with derivatives of 2-aminothiazoles (L1 = 2-amino-6-methylbenzothiazole, L2 = 2-amino-6-chlorobenzothiazole), general formula [PdL 2 Cl 2 ] were synthesized and characterized by elemental microanalyses, IR, NMR spectroscopy and X-ray spectroscopy in case of [Pd(L2) 2 Cl 2 ]. The kinetic of the substitution reactions of complexes and the nucleophiles, such as guanosine-5′-monophosphate (5'-GMP), tripeptide glutathione (GSH) and amino acid L-methionine (L-Met), were studied by stopped-flow technique. The complex C2 was always more reactive, while the order of the reactivity of the nucleophiles, due to the associative mode of the reaction, was L-Met > GSH > 5'-GMP. In order to determine the type of interactions between palladium(II) complexes and calf thymus DNA (CT-DNA), we used electronic absorption spectroscopy, viscosity measurements, and fluorescence spectroscopic studies, while interactions with bovine serum albumin (BSA) were determined only with fluorescence spectroscopic studies. The observed results confirmed that both complexes bound to DNA by groove binding. The significantly strong interaction with BSA, especially for complex C2 , was also observed. In vitro cytotoxic activity was evaluated against four tumor cell lines, 4 T1, CT26, MDA-MB-468, HCT116 and mesenchymal stem cells (mMSC). C1 complex showed higher cytotoxic activity against CT26 cell line. Flow cytometry analysis showed that C1 stimulated apoptosis of tumor cells via inhibition of expression of antiapoptotic Bcl-2 molecule and decelerated proliferation by decreasing Cyclin-D and increasing expression of P21. In vitro antimicrobial activity for ligands and corresponding palladium(II) complexes was investigated by microdilution method and minimum inhibitory concentration (MIC) and minimum microbicidal concentration (MMC) were determined. Tested compounds exhibited selective and moderate activity. Newly complexes [PdL 2 Cl 2 ] (L1 = 2-amino-6-methylbenzothiazole, L2 = 2-amino-6-chlorobenzothiazole) were synthesized and characterized by elemental microanalysis, IR, 1H, 13C NMR and X-ray spectroscopy for [Pd(L2) 2 Cl 2 ]. The kinetic of the substitution reactions and interactions of complexes with calf thymus DNA and bovine serum albumin were determined. In vitro cytotoxic and antimicrobial activity were tested. [Display omitted] • Two new palladium(II) complexes were synthesized. • Characterization was performed by IR, 1H and 13C NMR and X-ray spectroscopy. • The kinetic of the substitution reactions were studied by stopped-flow technique. • The interactions of new complexes with calf thymus DNA and bovine serum albumin were investigated. • Cytotoxic and antimicrobial activities of palladium(II) complexes were evaluated. [ABSTRACT FROM AUTHOR]

Four Pt(II) complexes of the general formula [Pt(L)(5,6-epoxy-1,10-phen)], where L is an anion of either malonic acid (mal, Pt1), 2-methylmalonic acid (Me-mal, Pt2), 2,2-dimethylmalonic acid (Me 2 -mal, Pt3) or 1,1-cyclobutanedicarboxylic acid (CBDCA, Pt4) and 5,6-epoxy-1,10-phen is 5,6-epoxy-5,6-dihydro-1,10-phenanthroline, were synthesized and characterized by elemental microanalysis and different spectroscopic techniques. The crystal structure of anhydrous Pt3 complex was determined by single crystal X-ray diffraction. The in vitro anticancer activity of the platinum(II) complexes was investigated in human and murine cancer cell lines as well as in a normal murine cell line by MTT assay. The results show that the investigated platinum(II) complexes exhibit potent cytotoxic activity against murine breast carcinoma cells (4T1), human (HCT116) and murine (CT26) colorectal carcinoma cells. The Pt3 complex shows stronger selectivity against cancer cells compared to other platinum(II) complexes tested and thus exhibits beneficial antitumor activity, mainly by inducing apoptosis and inhibiting cell proliferation and migration. The Pt3 complex also exhibits significant in vivo antitumor activity in the orthotopical 4T1 tumor model without detected liver, kidney, lung, and heart toxicity. All the results indicate that these novel platinum(II) complexes have good antitumor activity on breast and colorectal cancer and have the potential to become possible candidates for cancer treatment. Complexes Pt1 - Pt4 possess significant in vitro cytotoxicity against murine 4T1, CT26 and human HCT116 cells. Pt3 demonstrates highest selectivity toward cancer cells, triggering apoptosis of 4T1 and CT26 cancer cells with inhibition of cell proliferation and migration. Murine breast cancer growth was inhibited after in vivo application of Pt3. [Display omitted] • Pt1- Pt4 possess significant in vitro cytotoxicity against 4T1, HCT116, CT26 cells. • Pt3 complex triggered apoptosis of breast and colorectal cancer cells. • Pt3 complex diminished metastasis capacity of cancer cells. • In vivo application of Pt3 inhibited murine breast cancer growth and progression. • In vivo treatment with Pt3 caused low general toxicity. [ABSTRACT FROM AUTHOR]