Novel half Salphen cobalt(III) complexes: synthesis, DNA binding and anticancer studies.

While platinum(II)-based drugs continue to be employed in cancer treatments, the escalating occurrence of severe side effects has spurred researchers to explore novel sources for potential therapeutic agents. Notably, cobalt(III) has emerged as a subject of considerable interest due to its ubiquitous role in human physiology. Several studies investigating the anticancer effects of Salphen complexes derived from cobalt(III) have unveiled intriguing antiproliferative properties. In a bid to enhance our understanding of this class of compounds, we synthesized and characterized two novel half Salphen cobalt(III) complexes. Both compounds exhibited notable stability, even in the presence of physiologically relevant concentrations of glutathione. The application of spectroscopic and computational methodologies unravelled their interactions with duplex and G4-DNAs, suggesting an external binding affinity for these structures, with preliminary indications of selectivity trends. Importantly, antiproliferative assays conducted on 3D cultured SW-1353 cancer cells unveiled a compelling anticancer activity at low micromolar concentrations, underscoring the potential therapeutic efficacy of this novel class of cobalt(III) complexes.

How the Metal Ion Affects the 1H NMR Chemical Shift Values of Schiff Base Metal Complexes: Rationalization by DFT Calculations.

The chemical shift (CS) values obtained by 1H NMR spectroscopy for the hydrogen atoms of a tetradentate N2O2-substituted Salphen ligand (H2L1) are differently shifted in its complexes of nickel(II), palladium(II), platinum(II), and zinc(II), all bearing the same charge on the metal ions. To rationalize the observed trends, DFT calculations have been performed in the implicit d6-DMSO solvent in terms of the electronic effects induced by the metal ion and of the nature and strength of the metal-N and metal-O bonds. Overall, the results obtained point out that, in the complexes involving group 10 elements, the CS values show the greater shift when considering the two hydrogen atoms at a shorter distance from the coordinated metal center and follow the decreasing metal charge in the order Ni > Pd > Pt. This trend suggests a more covalent character of the ligand-metal bonds with the increase of the metal atomic number. Furthermore, a slightly poorer agreement between experimental and calculated data is observed in the presence of the nickel(II) ion. Such discrepancy is explained by the formation of stacked oligomers, aimed at minimizing the repulsive interactions with the polar DMSO solvent.

Salphen metal complexes as potential anticancer agents: interaction profile and selectivity studies toward the three G-quadruplex units in the KIT promoter.

DNA G-rich sequences can organize in four-stranded structures called G-quadruplexes (G4s). These motifs are enriched in significant sites within the human genomes, including telomeres and promoters of cancer related genes. For instance, KIT proto-oncogene promoter, associated with diverse cancers, contains three adjacent G4 units, namely Kit2, SP, and Kit1. Aiming at finding new and selective G-quadruplex binders, we have synthesized and characterized five non-charged metal complexes of Pt(II), Pd(II), Ni(II), Cu(II) and Zn(II) of a chlorine substituted Salphen ligand. The crystal structure of the Pt(II) and Pd(II) complexes was determined by XRPD. FRET measurements indicated that Pt(II) and Pd(II) compounds stabilize Kit1 and Kit2 G4s but not SP, telomeric and double stranded DNA. Spectroscopic investigations (UV-Vis, circular dichroism and fluorescence) suggested the Cu(II) complex as the most G4-selective compound. Interestingly, docking simulations indicate that the synthesized compounds fit groove binding pockets of both Kit1 and Kit2 G4s. Moreover, they exhibited dose-dependent cytotoxic activity in MCF-7, HepG2 and HeLa cancer cells.

Mononuclear Perfluoroalkyl-Heterocyclic Complexes of Pd(II): Synthesis, Structural Characterization and Antimicrobial Activity.

Two mononuclear Pd(II) complexes [PdCl2(pfptp)] (1) and [PdCl2(pfhtp)] (2), with ligands 2-(3-perfluoropropyl-1-methyl-1,2,4-triazole-5yl)-pyridine (pfptp) and 2-(3-perfluoroheptyl-1-methyl-1,2,4-triazole-5yl)-pyridine (pfhtp), were synthesized and structurally characterized. The two complexes showed a bidentate coordination of the ligand occurring through N atom of pyridine ring and N4 atom of 1,2,4-triazole. Both complexes showed antimicrobial activity when tested against both Gram-negative and Gram-positive bacterial strains.

Cytotoxic Activity of Organotin(IV) Derivatives with Triazolopyrimidine Containing Exocyclic Oxygen Atoms.

In this study cytotoxicity of organotin(IV) compounds with 1,2,4-triazolo[1,5-a]pyrimidines, Me3Sn(5tpO) (1), n-Bu3Sn(5tpO) (2), Me3Sn(mtpO) (3), n-Bu3Sn(mtpO) (4), n-Bu3Sn(HtpO2) (5), Ph3Sn(HtpO2) (6) where 5HtpO = 4,5-dihydro-5-oxo-[1,2,4]triazolo-[1,5-a]pyrimidine, HmtpO = 4,7-dihydro-5-methyl-7-oxo-[1,2,4]triazolo-[1,5-a]pyrimidine, and H2tpO2 = 4,5,6,7-tetrahydro-5,7- dioxo-[1,2,4]triazolo-[1,5-a]-pyrimidine, was assessed on three different human tumor cell lines: HCT-116 (colorectal carcinoma), HepG2 (hepatocarcinoma) and MCF-7 (breast cancer). While 1 and 3 were inactive, compounds 2, 4, 5 and 6 inhibited the growth of the three tumor cell lines with IC50 values in the submicromolar range and showed high selectivity indexes towards the tumor cells (SI > 90). The mechanism of cell death triggered by the organotin(IV) derivatives, investigated on HCT-116 cells, was apoptotic, as evident from the externalization of phosphatidylserine to the cell surface, and occurred via the intrinsic pathway with fall of mitochondrial inner membrane potential and production of reactive oxygen species. While compound 6 arrested the cell progression in the G2/M cell cycle phase and increased p53 and p21 levels, compounds 2, 4 and 5 blocked cell duplication in the G1 phase without affecting the expression of either of the two tumor suppressor proteins. Compounds 1 and 2 were also investigated using single crystal X-ray diffraction and found to be, in both cases, coordination polymers forming 1 D chains based on metal-ligand interactions. Interestingly, for n-Bu3Sn(5tpO)(2) H-bonding interactions between 5tpO- ligands belonging to adjacent chains were also detected that resemble the "base-pairing" assembly and could be responsible for the higher biological activity compared to compound 1. In addition, they are the first example of bidentate N(3), O coordination for the 5HtpO ligand on two adjacent metal atoms.

Quality evaluation of extra-virgin olive oils from Sicilian genotypes grown in a high-density system.

Studying the sensory profile and chemical composition of monovarietal extra-virgin olive oils (EVOOs) is important to define and manage their quality and uniqueness. Chemical and sensory traits of olive oils from 14 minor Sicilian olive genotypes in comparison with oils from six major Sicilian and three international cultivars were analysed. Oils were extracted in 2015 from fruit of the 23 genotypes grown in an experimental orchard at a planting density of 1140 trees ha-1. Fatty acid composition, phenol composition, carotenoid content and antioxidant power were determined and analysed using univariate and multivariate procedures, in particular Nocellara Etnea along with carotenoid, phenol content and good sensory attributes, producing the best quality EVOO among the genotypes in trial. These results show that some Sicilian accessions used in this study may represent valid alternatives to produce high-quality EVOOs in modern, hedgerow planting systems.

Anti-cancer activity of di- and tri-organotin(IV) compounds with D-(+)-Galacturonic acid on human tumor cells.

We have compared the anti-proliferative activity in vitro, of R2SnGala (1-3) [R = Me, n-Bu, Ph] and novel R3SnGala (4, 5) [R = Me, n-Bu] with D-(+)-Galacturonic acid [HGala; Galaq-, q = (2) and (1) for R2SnGala and R3SnGala, respectively] compounds, towards human tumor cell lines of intestinal carcinoma (HCT-116) and breast adenocarcinoma (MCF-7). The new synthesized 4 and 5 compounds were characterized, in solution, by 1H, 13C and 119Sn NMR, that showed that HGala acts as monoanionic moiety and evidenced the dynamic behavior of the compounds, due to inter-conversions involving the anomeric carbon atom of the ligand. Cell viability, apoptosis induction and cell cycle distribution were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay and flow cytometry, respectively. The cytotoxicity of the compounds, in the micro-submicromolar range, changed in the order of the organotin(IV) moieties, according to 5 > 3 > 2, while 1 and 4, containing MenSn(IV) (n = 2,3) moieties, were ineffective. Compound 5 showed peculiar cytotoxic effects. It did not cause time dependent inhibition of cell growth nor accumulated into the cells. Cell death induced by the active 2, 3, and 5, was shown to be apoptotic by measuring the exposure of phosphatidylserine to the outer membrane and the loss of mitochondrial potential. All the cytotoxic compounds induced an accumulation of cells in the subG0/G1phase, while only 2 and 3 perturbed the cell cycle confining viable cells in G0/G1phase. Finally, none of the compounds investigated affected the viability of normal intestinal or liver cells, indicating selectivity towards tumor cells.

Synthesis, properties, antitumor and antibacterial activity of new Pt(II) and Pd(II) complexes with 2,2'-dithiobis(benzothiazole) ligand.

Mono- and binuclear Pt(II) and Pd(II) complexes with 2,2'-dithiobis(benzothiazole) (DTBTA) ligand are reported. [Pt(DTBTA)(DMSO)Cl]Cl∙CHCl3 (1) and [Pd2(µ-Cl)2(DTBTA)2]Cl2 (2) have been synthesized and structurally characterized by elemental analysis, IR, 1H and 13C NMR spectroscopy, MS spectrometry and the content of platinum and palladium was determined using a flame atomic spectrometer. Two different coordination modes of 1 and 2 complexes were found; in both complexes, the coordination of Pt(II) and Pd(II) ions involves the N(3) atoms of the ligand but the binuclear complex 2, is a cis-chloro-bridged palladium complex. Evaluation of their in vitro antitumor activity against two human tumor cell lines human breast cancer (MCF-7) and hepatocellular carcinoma (HepG2); and their antimicrobial activity against Escherichia coli and Kokuria rhizophila was performed. Only complex 1 showed a dose- and time-dependent cytotoxic activity against the two tumor cell lines, associated to apoptosis and accumulation of treated cells in G0/G1 phase of cell cycle, while both 1 and 2 exhibited antimicrobial activity with complex 1 much more potent. The study on intracellular uptake in both MCF-7 and HepG2 cell lines revealed that only platinum of complex 1 is present inside the cells, suggesting a different mode of action of the two compounds. This was also in agreement with the results obtained for the antitumor and antibacterial activity.

Synthesis of platinum complexes with 2-(5-perfluoroalkyl-1,2,4-oxadiazol-3yl)-pyridine and 2-(3-perfluoroalkyl-1-methyl-1,2,4-triazole-5yl)-pyridine ligands and their in vitro antitumor activity.

Five new mononuclear Pt(II) complexes with 5-perfluoroalkyl-1,2,4-oxadiazolyl-pyridine and 3-perfluoroalkyl-1,2,4-triazolyl-pyridine ligands are reported. The ligands 2-(5-perfluoroheptyl-1,2,4-oxadiazole-3yl)-pyridine (pfhop), 2-(5-perfluoropropyl)-1,2,4-oxadiazole-3yl)-pyridine (pfpop), 2-(3-perfluoroheptyl-1-methyl-1,2,4-triazole-5yl)-pyridine (pfhtp), 2-(3-perfluoropropyl-1-methyl-1,2,4-triazole-5yl)-pyridine (pfptp) and their complexes [PtCl2(pfhop)2]·1.5 DMSO (2a), [PtCl2(pfpop)2]·1.5 DMSO (3a), [PtCl2(pfhtp)2]·1.5 DMSO (4a), PtCl2(pfhtp) (4b), [PtCl2(pfptp)2]·1.5 DMSO (5a) have been synthesized and structurally characterized. The complexes 2a, 3a, 4a and 5a have the same chemical environment of Pt(II) where PtCl2 moieties coordinate two molecules of ligand via N1 atom of pyridine in the case of pfhop and pfpop, and N2 atom of 1,2,4-triazole in the case of pfhtp and pfptp. For 4b, pfhtp behaves as bidentate ligand, coordinating Pt(II) ion via N4 atom of triazole and N1 atom of pyridine. All complexes have been tested in vitro by 3-(4,5-dimethyl-2-thiazolyl)bromide-2,5-diphenyl-2H-tetrazolium (MTT) test on four tumor cell lines MCF-7 (human breast cancer), HepG2 (human hepatocellular carcinoma), HCT116 (human colorectal carcinoma). Compounds 2a and 4b showed a dose-dependent anti-proliferative effect against the three tumor cell lines whereas did not affect viability of intestinal normal-like differentiated Caco-2 cells. The cell death of HepG2, MCF-7 and HCT116 induced by the compounds, was considered to be apoptotic by measuring the exposure of phosphatidylserine to the outer membrane and observing the typical apoptotic morphological change by acridine orange (AO)/ethidium bromide (EB) staining.

Synthesis, characterization, crystal structures and in vitro antistaphylococcal activity of organotin(IV) derivatives with 5,7-disubstituted-1,2,4-triazolo[1,5-a]pyrimidine.

New organotin(IV) complexes of 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp) and 5,7-diphenyl-1,2,4-triazolo[1,5-a]pyrimidine (dptp) with 1:1 and/or 1:2 stoichiometry were synthesized and investigated by X-ray diffraction, FT-IR and (119)Sn Mössbauer in the solid state and by (1)H and (13)C NMR spectroscopy, in solution. Moreover, the crystal and molecular structures of Et(2)SnCl(2)(dbtp)(2) and Ph(2)SnCl(2)(EtOH)(2)(dptp)(2) are reported. The complexes contain hexacoordinated tin atoms: in Et(2)SnCl(2)(dbtp)(2) two 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine molecules coordinate classically the tin atom through N(3) atom and the coordination around the tin atom shows a skew trapezoidal structure with axial ethyl groups. In Ph(2)SnCl(2)(EtOH)(2)(dptp)(2) two ethanol molecules coordinate tin through the oxygen atom and the 5,7-diphenyl-1,2,4-triazolo[1,5-a]pyrimidine molecules are not directly bound to the metal center but strictly H-bonded, through N(3), to the OH group of the ethanol moieties; Ph(2)SnCl(2)(EtOH)(2)(dptp)(2) has an all-trans structure and the C-Sn-C fragment is linear. On the basis of Mössbauer data, the 1:2 diorganotin(IV) complexes are advanced to have the same structure of Et(2)SnCl(2)(dbtp)(2), while Me(2)SnCl(2)(dptp)(2) to have a regular all-trans octahedral structure. A distorted cis-R(2) trigonal bipyramidal structure is assigned to 1:1 diorganotin(IV) complexes. The in vitro antibacterial activities of the synthesized complexes have been tested against a group of reference pathogen micro-organisms and some of them resulted active with MIC values of 5µg/mL, most of all against staphylococcal strains, which shows their inhibitory effect.