Vanadium Toxicological Potential Versus Its Pharmacological Activity: New Developments and Research

Scibior, A., Llopis, J., Holder, A. A., & Altamirano-Lozano, M. (2016). Vanadium toxicological potential versus its pharmacological activity: New developments and research. Oxidative Medicine and Cellular Longevity, 2016, 1-2. doi: 10.1155/2016/761234

Interesting Properties of p-, d-, and f-Block Elements When Coordinated With Dipicolinic Acid and Its Derivatives as Ligands: Their Use as Inorganic Pharmaceuticals

This is a review of the literature concerning the interesting properties of p-, d-, and f-block elements when coordinated with 2,6-pyridinedicarboxylic acid (dipicolinic acid, H2dipic) and its derivatives as ligands, with a focus on their use as inorganic pharmaceuticals. Some of the complexes reported were used as insulin-like, bioimaging contrasting agents, antimicrobial agents, and anticancer agents

A Novel Copper (II) Complex Identified as a Potent Drug Against Colorectal and Breast Cancer Cells and as a Poison Inhibitor for Human Topoisomerase IIᶐ

A novel complex, [Cu(acetylethTSC)Cl]Cl · 0.25C2H5OH 1 (where acetylethTSC = (E)-N-ethyl-2-[1-(thiazol-2-yl)ethylidene]hydrazinecarbothioamide), was shown to have anti-proliferative activity against various colon and aggressive breast cancer cell lines. In vitro studies showed that complex 1 acted as a poison inhibitor of human topoisomerase IIᶐ which may account for the observed anti-cancer effects

Synthesis and Characterization of Azo-Guanidine Based Alcoholic Media Naked Eye DNA Sensor

DNA sensing always has an open meadow of curiosity for biotechnologists and other researchers. Recently, in this field, we have introduced an emerging class of molecules containing azo and guanidine functionalities. In this study, we have synthesized three new compounds (UA1, UA6 and UA7) for potential application in DNA sensing in alcoholic medium. The synthesized materials were characterized by elemental analysis, FTIR, UV-visible, 1H NMR and 13C NMR spectroscopies. Their DNA sensing potential were investigated by UV-visible spectroscopy. The insight of interaction with DNA was further investigated by electrochemical (cyclic voltammetry) and hydrodynamic (viscosity) studies. The results showed that compounds have moderate DNA binding properties, with the binding constants range being 7.2 x 103, 2.4 x 103 and 0.2 x 103 M-1, for UA1, UA6 and UA7, respectively. Upon binding with DNA, there was a change in colour (a blue shift in the lambda(max) value) which was observable with a naked eye. These results indicated the potential of synthesized compounds as DNA sensors with detection limit 1.8, 5.8 and 4.0 ng μl-1 for UA1, UA6 and UA7, respectively

Synthesis, Characterization, and Cytotoxicity Studies of a Copper(II) Complex with vanillin 3-ethyl-thiosemcarbazone a Ligand

Triple-negative breast cancer (TNBC) is one of the most aggressive and challenging breast cancer subtypes to treat, as these cancer cells lack three common receptors: estrogen, progesterone, and human epidermal growth factor receptor 2. The multiple oxidation states transition metals can occupy have made this narrowly explored group popular for anti-cancer research in recent decades. Furthermore, the success of cisplatin, which has platinum as a metal center, while being a cancer-fighting agent with serious side effects, has caused other metal centers to be investigated as possible alternatives as chemotherapeutic drugs. Copper, as a biologically essential metal, makes an attractive candidate for a metal center in chemotherapeutic drugs. Additionally, metal-based compounds that contain thiosemicarbazones as ligands possess a wide range of biological activities. These ligands also have anti-cancer properties due to their ability to interfere with enzymes that catalyze DNA synthesis. Moreover, the biomedical activity of the thiosemicarbazones is enhanced by coordination to a transition metal center. Therefore, research involving thiosemicarbazones has become widespread due to their metal coordination capabilities. This study aims to synthesize, characterize, and utilize a copper(II) complex with vanillin 3-ethyl-thiosemcarbazone as a ligand in cytotoxicity studies. Elemental analysis, high resolution mass spectrometry, 1H NMR, 13C NMR, FTIR, and UV-visible spectroscopies will be utilized to characterize the complex. The cytotoxic activities of the complex will be determined using CCK-8 assay on the human TNBC cell line, MDA-MB-231-VIM RFP. Additionally, the MCF-10A human breast epithelial tissue cell line and cisplatin will be used as a controls in order to determine the efficacy of the complex

Anticancer Activity and Biophysical Reactivity of Copper Complexes of 2-(benzo[d][1,3]dioxol-5-ylmethylene)-N-Alkylhydrazinecarbothioamides

A series of copper complexes were synthesized from benzo[d][1,3]dioxole-5-carbaldehyde (piperonal) thiosemicarbazones (RHpTSC where R = H, CH3, C2H5 or C6H5 (Ph)). The complexes show interesting variations in geometry depending on the thiosemicarbazone; a dinuclear complex [Cu(HpTSC)Cl]2, a mononuclear complex [Cu(RHpTSC)2Cl2] (R = CH3 or C2H5) and another mononuclear complex [Cu(PhHpTSC)(PhpTSC)Cl] was generated. The complexes bind in a moderately strong fashion to DNA with binding constants on the order of 104 M− 1. They are also strong binders of human serum albumin with binding constants near 104 M− 1. The complexes show good in vitro cytotoxic profiles against two human colon cancer cell lines (HCT-116 and HT29) and two human breast cancer cell lines (MCF-7 and MDA-MB-231) with IC50 values in the low millimolar concentration range

Natural Phaeosphaeride A Derivatives Overcome Drug Resistance of Tumor Cells and Modulate Signaling Pathways

n the present study, natural phaeosphaeride A (PPA) derivatives are synthesized. Anti-tumor studies are carried out on the PC3, K562, HCT-116, THP-1, MCF-7, A549, NCI-H929, Jurkat, and RPMI8226 tumor cell lines, and on the human embryonic kidney (HEK293) cell line. All the compounds synthesized turned out to have better efficacy than PPA towards the tumor cell lines listed. Among them, three compounds exhibited an ability to overcome the drug resistance of tumor cells associated with the overexpression of the P-glycoprotein by modulating the work of this transporter. Luminex xMAP technology was used to assess the effect of five synthesized compounds on the activation of intracellular kinase cascades in A431 cells. MILLIPLEX MAP Multi-Pathway Magnetic Bead 9-Plex was used, which allowed for the simultaneous detection of the following nine phosphorylated protein markers of the main intracellular signaling pathways: a universal transcription factor that controls the expression of immune-response genes, apoptosis and cell cycle NFκB (pS536); cAMP-dependent transcription factor (CREB (pS133); mitogen-activated kinase p38 (pT180/pY182); stress-activated protein kinase JNK (pT183/pY185); ribosomal SK; transcription factors STAT3 (pS727) and STAT5A/B (pY694/699); protein kinase B (Akt) (pS473); and kinase regulated by extracellular signals ERK1/2 (pT185/pY187). The effect of various concentrations of PPA derivatives on the cell culture was studied using xCelligence RTCA equipment. The compounds were found to modulate JNK, ERK1/2, and p38 signaling pathways. The set of activated kinase cascades suggests that oxidative stress is the main probable mechanism of the toxic action of PPA derivatives

Novel Survivin Inhibitor for Suppressing Pancreatic Cancer Cells Growth via Downregulating Sp1 and Sp3 Transciption Factors

Background/Aims: Targeting survivin, an anti-apoptotic protein and mitotic regulator, is considered as an effective therapeutic option for pancreatic cancer (PaCa). Tolfenamic acid (TA) showed anti-cancer activity in pre-clinical studies. A recent discovery demonstrated a copper(II) complex of TA (Cu-TA) can result in higher activity. In this study, the ability of Cu-TA to inhibit survivin and its transcription factors, Specificity protein (Sp) 1 and 3 in PaCa cell lines and tumor growth in mouse xenograft model were evaluated. Methods: Cell growth inhibition was measured in MIA PaCa-2 and Panc1 cells for 2 days using CellTiter-Glo kit. Sp1, Sp3 and survivin expression (by Western blot and qPCR), apoptotic cells and cell cycle phase distribution (by flow cytometry) were evaluated. A pilot study was performed using athymic nude mice [treated with vehicle/Cu-TA (25 or 50 mg/kg) 3 times/week for 4 weeks. Results: The IC50 value for Cu-TA was about half than TA. Both agents repressed the protein expression of Sp1/Sp3/survivin, Cu-TA was more effective than TA. Especially effect on survivin inhibition was 5.2 (MIA PaCa-2) or 6.4 (Panc1) fold higher and mRNA expression of only survivin was decreased. Apoptotic cells increased with Cu-TA treatment in both cell lines, while Panc1 showed both effect on apoptosis and cell cycle (G2/M) arrest. Cu-TA decreased the tumor growth in mouse xenografts (25 mg/kg: 48%; 50 mg/kg: 68%). Additionally, there was no change observed in mice body weights, indicating no overt toxicity was occurring. Conclusion: These results show that Cu-TA can serve as an effective survivin inhibitor for inhibiting PaCa cell growth

Anticancer, Biophysical and Computational Investigations of Half-Sandwich Ruthenium(II) Thiosemicarbazone Complexes: The Effect of Arene \u3ci\u3eVersus\u3c/i\u3e Thiacrown Face-Cap

A series of half-sandwich ruthenium complexes, two containing an arene face-cap and the other a thiacrown ether face-cap were synthesized to investigate the necessity of the arene for anticancer activity in this class of compounds. The complexes are formulated as [(h6-p-cymene)Ru(dmabTSC)Cl]PF6, [(h6-benzene)Ru(dmabTSC)Cl]PF6 (arene complexes), and [([9]aneS3(dmabTSC)Cl]PF6 (dmabTSC = dimethylaminobenzaldehye thiosemicarbazone). It was observed that none of the complexes showed good anticancer activity in vitro against HCT-116 and Caco-2 (colon adenocarcinoma) cells. All three complexes can bind strongly to calf-thymus DNA with binding constants on the order of 105 M-1. In addition they all bind strongly to human serum albumin with binding constants between 105 and 106 M-1. There appears to be a single binding site on the protein for these complexes. A computational investigation of these complexes and their hydrolysis products was carried out by molecular docking with DNA and topoisomerase II. From this analysis it is noted that the type of face-capping ligand had different effects on the two macromolecules. It is therefore noted that the knowledge gained from this study will be useful in identifying the type of complexes in this class that show useful metallodrug potential

Effects of Metal Compounds with Distinct Physicochemical Properties on Iron Homeostasis and Antibacterial Activity in the Lungs: Chromium and Vanadium

In situ reactions of metal ions or their compounds are important mechanisms by which particles alter lung immune responses. The authors hypothesized that major determinants of the immunomodulatory effect of any metal include its redox behavior/properties, oxidation state, and/or solubility, and that the toxicities arising from differences in physicochemical parameters are manifest, in part, via differential shifts in lung iron (Fe) homeostasis. To test the hypotheses, immunomodulatory potentials for both pentavalent vanadium (V(V); as soluble metavanadate or insoluble vanadium pentoxide) and hexavalent chromium (Cr(VI); as soluble sodium chromate or insoluble calcium chromate) were quantified in rats after inhalation (5 h/day for 5 days) of each at 100 mu g metal/m(3). Differences in effects on local bacterial resistance between the two V(V), and between each Cr(VI), agents suggested that solubility might be a determinant of in situ immunotoxicity. For the soluble forms, V(V) had a greater impact on resistance than Cr(VI), indicating that redox behavior/properties was likely also a determinant. The soluble V(V) agent was the strongest immunomodulant. Regarding Fe homeostasis, both V(V) agents had dramatic effects on airway Fe levels. Both also impacted local immune/airway epithelial cell Fe levels in that there were significant increases in production of select cytokines/chemokines whose genes are subject to regulation by HIF-1 (whose intracellular longevity is related to cell Fe status). Our findings contribute to a better understanding of the role that metal compound properties play in respiratory disease pathogenesis and provide a rationale for differing pulmonary immunotoxicities of commonly encountered ambient metal pollutants