Development of an Efficient Dual‐Action GST‐Inhibiting Anticancer Platinum(IV) Prodrug

The cytotoxicity of cisplatin (cDDP) is enhanced when co‐administered with ethacrynic acid (EA), a glutathione S‐transferase (GST) inhibitor. A Pt^IV–EA conjugate containing a cDDP core and two axial ethacrynate ligands (compound 1 ) was shown to be an excellent inhibitor of GST, but did not readily release a Pt^II species to exert a synergistic cytotoxic effect. In this study, a redesigned Pt^IV construct composed of a cDDP core with one axial ethacrynate ligand and one axial hydroxido ligand (compound 2 ) was prepared and shown to overcome the limitations of compound 1 . The EA ligand in 2 is readily released in vitro together with a cytotoxic Pt^II species derived from cisplatin, working together to inhibit cell proliferation in cDDP‐resistant human ovarian cancer cells. The in vitro activity translates well in vivo with 2 , showing effective (～80 %) inhibition of tumor growth in a human ovarian carcinoma A2780 tumor model, while showing considerably lower toxicity than cisplatin, thus validating the new design strategy.     

Platinum(II) Complexes Bearing Triphenylphosphine and Chelating Oximes: Antiproliferative Effect and Biological Profile in Resistant Cells

Platinum(II) complexes of the type [Pt(Cl)(PPh₃){(κ²-N,O)-(1{C(R)=N(OH)-2(O)C₆H₄})}] with R=Me, H, ( 1 and 2 ) were synthesized and characterized. Single-crystal X-ray diffraction confirmed the proposed (SP4-3) configuration for 1 . Study of the antiproliferative activity, performed on a panel of human tumor cell lines and on mesothelial cells, highlighted complex 2 as the more effective. In particular, it showed a remarkable cytotoxicity in ovarian carcinoma cells (A2780) and interestingly, a significant antiproliferative effect on cisplatin resistant cells (A2780cis). Investigation into the intracellular mechanism of action demonstrated that 2 had a lower ability to platinate DNA than did cisplatin, which was taken as reference, and a notably higher uptake in resistant cells. A significant accumulation in mitochondria, along with the ability to induce concentration-dependent mitochondrial membrane depolarization and intracellular reactive oxygen species production, allowed us to propose a mitochondrion-mediated pathway as responsible for the interesting cytotoxic profile of complex 2 .     

Studies on the Synthesis and Activity of Three Tripalladium Complexes Containing Planaramine Ligands

The present study deals with the synthesis, characterization and activity against human cancer cell lines: A2780, A2780^cisR and A2780^ZD0473R of three tripalladium complexes, MH3, MH4 and MH5, that each have two planaramine ligands bound to the central metal ion. Cellular uptake levels, extent of DNA binding, and nature of interaction with salmon sperm and pBR322 plasmid DNA were determined for each complex. Palladium compounds are much more reactive than their corresponding platinum derivatives, which makes them therapeutically inactive but toxic. However, the results of the present study suggest that significant antitumour activity can be introduced in palladium complexes by lessening their reactivity by the introduction of sterically hindered ligands such as 2‐hydroxypyridine, 3‐hydroxypyridine and 4‐hydroxypyridine. When bound to the central palladium ion, 4‐hydroxypyridine appears to be more activating than 2‐hydroxypyridine and 3‐hydroxypyridine, suggesting that noncovalent interactions, such as hydrogen bonding, may also be key determinants of antitumour activity in addition to the steric effect. While cisplatin binds with DNA to form intrastrand GG adducts that causes local bending of a DNA strand, these planaramine‐derived palladium complexes are expected to bind with DNA and form a number of long‐range interstrand GG adducts that would cause a global change in DNA conformation, provided the tripalladium cations in MH3, MH4 and MH5 persist under physiological conditions.     

Cellular Uptake, DNA Binding and Apoptosis Induction of Cytotoxic Trans-[PtCl(2)(N,N-dimethylamine)(Isopropylamine)] in A2780cisR Ovarian Tumor Cells

Trans-[PtCl(2)(N,N-dimethylamine)(isopropylamine)] is a novel trans-platinum compound that shows cytotoxic activity in several cisplatin resistant cell lines. The aim of this paper was to analyse, by means of molecular cell biology techniques and total reflection X-ray fluorescence (TXRF), the cytotoxic activity, the induction of apoptosis, the cellular uptake and the DNA binding of trans-[PtCl(2)(N,N-dimethylamine)(isopropylamine)] in the cisplatin resistant cell line A2780cisR. The results show that this drug is more cytotoxic and induces a higher amount of apoptotic cells than cisplatin in A2780cisR cells. However, the intracellular accumulation and extent of binding to DNA of trans-[PtCl(2)(N,N-dimethylamine)( isopropylamine)] is lower than that of cis-DDP. Moreover, trans-[PtCl(2)(N,N-dimethylamine)(isopropylaminae)] is partially inactivated by intracellular levels of glulathione. The result suggest that circumvention of ciplatin resistance by trans-[PtCl(2)(N,N-dimethylamine)(isopropylamine)] in A2780cisR cells might be related with the ability of this drug to induce apoptosis.     

In Situ Soft X‐ray Microscopy Study of Fe Interconnect Corrosion in Ionic Liquid‐Based Nano‐PEMFC Half‐Cells

This in situ soft X‐ray scanning microscopy electrochemical study of model proton exchange cathodic and anodic nano‐fuel cells is exploring the evolving structure and chemical composition of key cell components represented by Au and Fe electrodes in contact with Nafion‐ionic liquid composite electrolyte containing Pt black catalyst particles. Morphological and chemical changes of the electrodes as well as the chemical state and fate of the Fe species released into the electrolyte are monitored in short circuit and with applied cathodic or anodic polarization. The in situ X‐ray absorption images of the cathodic cell fed with 2.5 × 10^–5 mbar O₂ have revealed corrosion‐induced morphology changes in the Fe electrode, being more pronounced in the vicinity of Pt‐black particles, and deposition of the Fe species released into the electrolyte, onto the intact Au counter electrode upon cathodic polarization. The Fe electrodes of the anodic cell containing NaBH₄ in the electrolyte appear relatively more corrosion resistant. The Fe L₃ absorption spectra taken in different locations within the Fe electrode have shown lateral variations in the relative ratio between Fe²⁺ and Fe^3&4+ oxidation states, whereas the Fe species released into the RTIL electrolyte are only in the high Fe^3&4+ oxidation states.     

Proteins as Possible Targets for Cytotoxic trans‐Platinum(II) Complexes with Aliphatic Amine Ligands: Further Exceptions to the DNA Paradigm

The reactivity of three cytotoxic trans‐Pt^II complexes bearing aliphatic amine ligands, with transferrin and single‐stranded oligonucleotides as DNA models, was investigated by ESI‐MS and the results obtained are discussed in comparison with cisplatin. Tandem MS studies provided additional information on the preferential Pt binding sites. To determine whether trans‐Pt^II complexes can migrate from a peptide to an oligonucleotide, transfer experiments were also performed using ESI‐MS, and competitive binding of the trans‐Pt^II complexes toward a model peptide and different oligonucleotides was also investigated. Significant differences in the reactivity of the trans complexes with respect to cisplatin were observed. In general, adduct formation with the selected peptide is favored for the trans compounds, whereas cisplatin shows a preference for oligonucleotides, especially if adjacent G–G residues are present. The results are discussed in relation to the possible mechanism of action of the trans‐Pt^II complexes.     

Polyaniline–13X zeolite composite‐supported platinum electrocatalysts for direct methanol fuel cell applications

We successfully synthesized 13X zeolite using a hydrothermal method. Then, composites of polyaniline (PANI) with 13X zeolite and PANI–13X with platinum were prepared by chemical oxidative polymerization and chemical reduction, respectively. Field emission scanning electron microscopy, X‐ray diffraction, Raman spectroscopy and Brunauer–Emmett–Teller techniques were used to characterize the PANI–Pt and PANI–Pt–13X composites. Further, the electrocatalytic activity towards methanol oxidation of the synthesized catalysts was explored using cyclic voltammetry in 1 mol L^?1 CH₃OH + 0.5 mol L^?1 H₂SO₄ solution. From the obtained results, PANI–Pt–13X shows superior performance compared to PANI–Pt towards methanol oxidation and electrical conductivity. Hence, the 13X zeolite‐incorporated PANI–Pt composite could be an efficient catalyst for direct methanol fuel cell applications. © 2019 Society of Chemical Industry     

Design and Synthesis of DNA‐Interactive β‐Carboline–Oxindole Hybrids as Cytotoxic and Apoptosis‐Inducing Agents

A new series of (E)‐3‐[(1‐aryl‐9H‐pyrido[3,4‐b]indol‐3‐yl)methylene]indolin‐2‐one hybrids were synthesized and evaluated for their in vitro cytotoxic activity against a panel of selected human cancer cell lines, namely, HCT‐15, HCT‐116, A549, NCI‐H460, and MCF‐7, including HFL. Among the tested compounds, (E)‐1‐benzyl‐5‐bromo‐3‐{[1‐(2,5‐dimethoxyphenyl)‐9H‐pyrido[3,4‐b]indol‐3‐yl]methylene}indolin‐2‐one ( 10 s ) showed potent cytotoxicity against HCT‐15 cancer cells with an IC₅₀ value of 1.43±0.26 μm and a GI₅₀ value of 0.89±0.06 μm . Notably, induction of apoptosis by 10 s on the HCT‐15 cell line was characterized by using different staining techniques, such as acridine orange/ethidium bromide (AO/EB) and DAPI. Further, to understand the mechanism of anticancer effects, various assays such as annexin V‐FITC/PI, DCFDA, and JC‐1were performed. The flow cytometric analysis revealed that compound 10 s arrests the HCT‐15 cancer cells at the G0/G1 phase of the cell cycle. Additionally, western blot analysis indicated that treatment of 10 s on HCT‐15 cancer cells led to decreased expression of anti‐apoptotic Bcl‐2 and increased protein expression of both pro‐apoptotic Bax and caspase‐3, ‐8, and ‐9, and cleaved PARP with reference to actin. Next, a clonogenic assay revealed the inhibition of colony formation in HCT‐15 cancer cells by 10 s in a dose‐dependent manner. Moreover, upon testing on normal human lung cells (HFL), the compounds were observed to be safer with a low toxicity profile. In addition, viscosity and molecular‐docking studies showed that compound 10 s has typical intercalation with DNA.     

Synergistic effect and drug‐resistance relief of paclitaxel and cisplatin caused by Co‐delivery using polymeric micelles

Combination therapy of paclitaxel (PTX) and cisplatin has been used to treat several cancers in clinic practice, but often causes serious systemic toxicity. Co‐delivery of PTX and cisplatin by means of polymeric micelles can reduce the systemic toxicity, but often needs two carrier polymers because of the solubility difference between them. Therefore, a strategy is developed to co‐deliver both PTX and cisplatin with only one carrier polymer by encapsulating PTX in the core of a polymeric micelle and cross‐linking the micelle with cisplatin. The PTX and Pt contents in the micellar formulation M(PTX/Pt) were 10 and 14 wt %, respectively. In vitro cytotoxicity of M(PTX/Pt) was evaluated via 3‐(4,5‐dimethylthiazol‐2‐yl)?2,5‐diphenyltetrazolium bromide assay in comparison with PTX and its micelle M(PTX), cisplatin and its micelle M(Pt), and PTX/cisplatin combination towards human hepatocarcinoma (SMMC‐7721) cells and chemoresistant SMMC‐7721(SMMC‐7721R) cells. The M(PTX/Pt) exhibited a high synergistic effect in the inhibition of cell growth and proliferation of both SMMC‐7721 and SMMC‐7721R cells and showed reasonable drug‐resistance relief. The synergistic effect and resistance relief were further supported or explained by intracellular uptake measurement of dye‐labeled micelles and by the confocal laser scanning microscopy observation of SMMC‐7721 and SMMC‐7721R cells treated with various formulations. Therefore, M(PTX/Pt) micelles were expected to find potential application in cancer chemotherapy. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41440.     

Electropreparation of (±)‐10‐camphorsulfonate‐doped poly(o‐phenylenediamine) in acetonitrile and its use in determination of glucose

Poly(o‐phenylenediamine) (PoPD) film has been electrochemically prepared on Pt electrode in an acetonitrile–water medium containing o‐phenylenediamine (oPD) monomer and (±)‐10‐camphorsulfonic acid (HCSA) by using the cyclic voltammetry (CV). The PoPD film (PoPD–CSA) has been characterized by FTIR, CV, EIS, FESEM, and conductivity measurement. The glucose biosensor (Pt/PoPD–CSA/GOx) has been prepared from the PoPD coated electrode by immobilizing glucose oxidase (GOx) enzyme using glutaraldehyde. The biosensor shows a low detection limit and wide linear working range, a good reusability, long‐term stability, and anti‐interference ability. The Pt/PoPD–CSA/GOx has possesses higher sensitivity (2.05 μA/mmol L^?1) and affinity to glucose due to the use of CSA ion as dopant. The linear concentration ranges of Pt/PoPD–CSA/GOx have been found to be 9.6 × 10^?3 to 8.2 mmol L^?1 from calibration curve and 4.6 × 10^?2 to 100 mmol L^?1 from the relationship between the (1/glucose concentration) and (1/current difference). © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39864.     

Two‐Face,Two‐Turn α‐Helix Mimetics Based on a Cross‐Acridine Scaffold: Analogues of the Bim BH3 Domain

The design of a cross‐acridine scaffold mimicking the i, i+3, i+5, and i+7 residues distributed over a two‐face, two‐turn α‐helix is described. Docking studies and 2D ¹H,¹⁵N HSQC NMR spectroscopy provide compelling evidence that compound 3 d accurately reproduces the arrangement of four hotspots in the Bim BH3 peptide to permit binding to the Mcl‐1 and Bcl‐2 proteins (K_i 0.079 and 0.056 μM , respectively). Furthermore, the hotspot mutation could also be mimicked by individual or multiple deletions of side chains on the scaffold.     

Cell‐Selective,Apoptosis‐inducing Rhodium(III) Crown Thiaether Complexes

Half‐sandwich rhodium(III) polypyridyl (pp) complexes with the metal atom capped by the facial crown thiaether 1,4,7‐trithiacyclononane [9]aneS₃ represent a promising class of apoptosis‐inducing potent cytostatic agents. The necrotic damage caused by the complexes is negligible. In vitro cytotoxicity assays with the human cancer cell lines MCF‐7 and HT‐29 and immortalized HEK‐293 cells indicate that the dicationic κ²N(imino) complexes [([9]aneS₃)RhCl(pp)]²⁺ are much more active than monocationic complexes [([9]aneS₃)RhCl₂(L)]⁺ (L=imidazole, CH₃CN). Whereas the κ²N(amino) complex [([9]aneS₃)RhCl(piperazine)]²⁺ is inactive, replacing piperazine with the structurally analogous κ²S (thiaether) ligand 1,4‐dithiane restores cytotoxicity as evidenced by IC₅₀ values in the range 8.1‐11.6 μM . Spectroscopic (CD, UV/Vis, NOESY) and viscosity measurements indicate that the active dppz complex 8 (IC₅₀ values: 4.7–8.9 μM ) exhibits strong intercalative binding towards DNA whereas the even more potent bipyrimidine complex 9 (IC₅₀ values: 0.6–1.9 μM ) causes no alteration of the duplex B conformation. Weaker intercalative binding is observed for the dpq complex 7 . A comparative annexin V–propidium iodide binding assay with lymphoma (BJAB) cells and healthy leukocytes demonstrates that the cytotoxic activity of complex 8 and particularly complex 9 is highly selective towards the malignant cells.     

Synthesis and in vitro Anticancer Activity of Octahedral Platinum(IV) Complexes with Cyclohexyl‐Functionalized Ethylenediamine‐N,N′‐Diacetate‐Type Ligands

The present study describes the synthesis and anticancer activity of novel octahedral Pt^IV complexes with cyclohexyl functionalized ethylenediamine‐N,N′‐diacetate‐type ligands. Molecular mechanics calculations and density functional theory analysis revealed that s‐cis is the preferred geometry of these Pt^IV complexes with tetradentate‐coordinated (S,S)‐ethylenediamine‐N,N′‐di‐2‐(3‐cyclohexyl)propanoate. The viability of cancer cell lines (U251 human glioma, C6 rat glioma, L929 mouse fibrosarcoma, and B16 human melanoma) was assessed by measuring mitochondrial dehydrogenase activity and lactate dehydrogenase release. Cell‐cycle distribution, oxidative stress, caspase activation, and induction of autophagy were analyzed by flow cytometry using appropriate fluorescent reporter dyes. The cytotoxic activity of novel Pt^IV complexes against various cancer cell lines (IC₅₀ range: 1.9–8.7 μM ) was higher than that of cisplatin (IC₅₀ range: 10.9–67.0 μM ) and proceeded through completely different mechanisms. Cisplatin induced caspase‐dependent apoptosis associated with the cytoprotective autophagic response. In contrast, the new Pt^IV complexes caused rapid, caspase‐independent, oxidative stress‐mediated non‐apoptotic cell death characterized by massive cytoplasmic vacuolization, cell membrane damage, and the absence of protective autophagy.     

DNA interstrand cross-linking efficiency and cytotoxic activity of novel cadmium(II)-thiocarbodiazone complexes

We have prepared mono- and binuclear complexes of Zn(II) and Cd(II) with bis(2-pyridyl aldehyde) thiocarbodiazone (H(2)L(1)) and bis(methyl 3-pyridyl ketone) thiocarbodiazone (H(2)L(2)). Cytotoxicity data against the ovarian tumor cell line A2780cisR (acquired resistance to cisplatin) indicate that the mononuclear complex Cd/H(2)L(2) (1) and the binuclear complex Cd(2)/H(2)L(1) (4) are able to circumvent cisplatin resistance and that their cytotoxic activity does not substantially vary after depletion of intracellular levels of glutathione. Moreover, DNA binding studies show that complexes 1 and 4 have higher efficiency than cisplatin at forming DNA interstrand cross-links in both naked pBR322 plasmid and A2780cisR cellular DNA. Interestingly, the thiocarbodiazone ligands alone do not show the biological properties of complexes 1 and 4. Altogether these results suggest that DNA interstrand cross-link formation by compounds 1 and 4 might be related with their cytotoxic activity in cisplatin-resistant cells. We think that compounds 1 and 4 may represent a novel structural lead for the development of cadmium cytotoxic agents capable of improving antitumor activity in cisplatin-resistant tumors.     

Development of 3‐Phenyl‐N‐(2‐(3‐phenylureido)ethyl)‐thiophene‐2‐sulfonamide Compounds as Inhibitors of Antiapoptotic Bcl‐2 Family Proteins

Antiapoptotic Bcl‐2 family proteins, such as Bcl‐x_L, Bcl‐2, and Mcl‐1, are often overexpressed in tumor cells, which contributes to tumor cell resistance to chemotherapies and radiotherapies. Inhibitors of these proteins thus have potential applications in cancer treatment. We discovered, through structure‐based virtual screening, a lead compound with micromolar binding affinity to Mcl‐1 (inhibition constant (K_i)=3 μM ). It contains a phenyltetrazole and a hydrazinecarbothioamide moiety, and it represents a structural scaffold not observed among known Bcl‐2 inhibitors. This work presents the structural optimization of this lead compound. By following the scaffold‐hopping strategy, we have designed and synthesized a total of 82 compounds in three sets. All of the compounds were evaluated in a fluorescence‐polarization binding assay to measure their binding affinities to Bcl‐x_L, Bcl‐2, and Mcl‐1. Some of the compounds with a 3‐phenylthiophene‐2‐sulfonamide core moiety showed sub‐micromolar binding affinities to Mcl‐1 (K_i=0.3–0.4 μM ) or Bcl‐2 (K_i≈1 μM ). They also showed obvious cytotoxicity on tumor cells (IC₅₀<10 μM ). Two‐dimensional heteronuclear single quantum coherence NMR spectra of three selected compounds, that is, YCW‐E5, YCW‐E10, and YCW‐E11, indicated that they bind to the BH3‐binding groove on Bcl‐x_L in a similar mode to ABT‐737. Several apoptotic assays conducted on HL‐60 cells demonstrated that these compounds are able to induce cell apoptosis through the mitochondrial pathway. We propose that the compounds with the 3‐phenylthiophene‐2‐sulfonamide core moiety are worth further optimization as effective apoptosis inducers with an interesting selectivity towards Mcl‐1 and Bcl‐2.     

DNA interaction and cytotoxic activity of copper complex based on tridentate hydrazone derived ligand and nitrogen donor heterocycle

Tetra coordinated copper(II) complex of formula [Cu(L¹)(imid)] is synthesized using imidazole and a tridentate O,N,O hydrazone ligand L¹ prepared by condensation of 1,1,1-trifluoropentanedione and 4-chlorobenzhydrazide. The ligand and complex are characterized by UV–Visible, FTIR, NMR, mass and single crystal XRD techniques. DNA binding mode is assessed by UV absorption, fluorescence spectral and circular dichroism studies. Based on the results, it is observed that complex has preferred intercalative mode of binding with DNA. The binding constant, K_b, was found to be 4.02 ± 0.09 × 10⁴ M^− 1. Thermodynamic parameters such as ΔH, ΔS and ΔG obtained from acridine orange fluorescence displacement assay revealed that the hydrophobic and hydrogen bonding interactions are playing a major role in the binding pattern. In addition, cytotoxicity of the complex towards MCF-7 breast cancer cell line has also been assessed.     

Non‐natural Peptide Triazole Antagonists of HIV‐1 Envelope gp120

We investigated the derivation of non‐natural peptide triazole dual receptor site antagonists of HIV‐1 Env gp120 to establish a pathway for developing peptidomimetic antiviral agents. Previously we found that the peptide triazole HNG‐156 [R‐I‐N‐N‐I‐X‐W‐S‐E‐A‐M‐M‐CONH₂, in which X=ferrocenyltriazole‐Pro (FtP)] has nanomolar binding affinity to gp120, inhibits gp120 binding to CD4 and the co‐receptor surrogate mAb 17b, and has potent antiviral activity in cell infection assays. Furthermore, truncated variants of HNG‐156, typified by UM‐24 (Cit‐N‐N‐I‐X‐W‐S‐CONH₂) and containing the critical central stereospecific ^LX‐^LW cluster, retain the functional characteristics of the parent peptide triazole. In the current work, we examined the possibility of replacing natural with unnatural residue components in UM‐24 to the greatest extent possible. The analogue with the critical “hot spot” residue Trp 6 replaced with L ‐3‐benzothienylalanine (Bta) (KR‐41), as well as a completely non‐natural analogue containing D ‐amino acid substitutions outside the central cluster (KR‐42, ^DCit‐^DN‐^DN‐^DI‐X‐Bta‐^DS‐CONH₂), retained the dual receptor site antagonism/antiviral activity signature. The results define differential functional roles of subdomains within the peptide triazole and provide a structural basis for the design of metabolically stable peptidomimetic inhibitors of HIV‐1 Env gp120.     

Pre-Treatment of Platinum Resistant Ovarian Cancer Cells with an MMP-9/MMP-2 Inhibitor Prior to Cisplatin Enhances Cytotoxicity as Determined by High Content Screening

Platinum resistance is a major cause of treatment failure in ovarian cancer. We previously identified matrix metalloproteinase 9 (MMP-9) as a potential therapeutic target of chemoresistant disease. A2780cis (cisplatin-resistant) and A2780 (cisplatin-sensitive) ovarian carcinoma cell lines were used. The cytotoxic effect of MMP-9/MMP-2 inhibitor, (2R)-2-[(4-Biphenylsulfonyl) amino]-3 phenylpropionic acid (C21H19NO4S) alone or in combination with cisplatin was determined using high content screening. Protein expression was examined using immunohistochemistry and ELISA. Co-incubation of cisplatin and an MMP-9/MMP-2 inhibitor, (2R)-2-[(4-Biphenylsulfonyl) amino]-3 phenylpropionic acid (C21H19NO4S) resulted in significantly greater cytotoxicity as compared to either treatment alone in a cisplatin resistant MMP-9 overexpressing cell line; A2780cis. In addition, pre-incubating with MMP-9i prior to cisplatin further enhances the cytotoxic effect. No significant difference was observed in MMP-9 protein in tissue but a trend towards increased MMP-9 was observed in recurrent serum. We propose that MMP-9/MMP-2i may be utilized in the treatment of recurrent/chemoresistant ovarian cancers that overexpress MMP-9 mRNA but its role in vivo remains to be evaluated.     

Enhancement of electrodes modified by electrodeposited PEDOT‐nanowires with dispersed Pt nanoparticles for formic acid electro‐oxidation

Preparation of electrodes modified with poly(3,4‐ethylenedioxythiophene) nanowires, PEDOT‐nw, was optimized using nanoparticles of dispersed Pt, Pt‐np, to be tested for HCOOH electro‐oxidation. The PEDOT‐nw is electrosynthesized directly on the working electrode, using mesoporous silica as template, by cyclic voltammetry from a 0.01 mol L^?1 monomer + 0.1 mol L^?1 tetrabutylammonium hexafluorophosphate solution in acetonitrile, on the Pt|PEDOT|mesoporous silica template previously modified electrodes. Using SEM, the presence of PEDOT nanowires with 20 to 25 nm in diameter was verified. In addition, its p ‐doping response is about 500 times larger than that obtained on the bulk polymer, maintaining full reversibility of the process. The subsequent electrochemical insertion of Pt‐np and formation of Pt‐np with average diameter of about 20 nm, checked by TEM, demonstrated that the catalytic activity of this nanostructured electrode remarkably enhanced HCOOH electro‐oxidation. The obtained current is up to 2 orders of magnitude higher than previously reported in similar studies, using a much smaller amount of Pt and with a potential decrease greater than 100 mV. Thus, we have at our disposal a simple, inexpensive, and highly reproducible way to prepare in situ nanostructured electrodes using just electrochemical techniques, which can be useful on all the applications of these devices. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134 , 44723.     

Synthesis and activity of a trinuclear platinum complex: [{trans-PtCl(NH3)2}2mu-{trans-Pt(3-hydroxypyridine)2(H2N(CH2)6NH2)2}]Cl4 in ovarian cancer cell lines

This paper describes the synthesis, characterisation, and cytotoxicity of a novel trinuclear platinum complex code named TH1. In addition to its activity against human ovarian cancer cell lines: A2780, A2780(cisR), and A2780(ZD0473R), cell uptake, DNA-binding, and the nature of the compound interaction with pBR322 plasmid DNA have been determined. TH1 is found to be significantly more cytotoxic than cisplatin - two times more active than cisplatin against the parent cell line A2780, thirteen times more active against the cisplatin-resistant cell line A2780(cisR) and 11.5 times more active against the cell line A2780(ZD0473R). Whereas the resistance factors for cisplatin as applied to the cell lines A2780 and A2780(cisR), and A2780 and A2780(ZD0473R) are 12.9 and 3.0 respectively, the corresponding values for TH1 are 1.98 and 0.5. The results suggest that TH1 has been able to significantly overcome resistance in A2780(cisR) and A2780(ZD0473R) cell lines. Whereas cisplatin binds with DNA forming mainly intrastrand GG adduct that causes local bending of a DNA strand, TH1 should bind with DNA forming mainly interstrand GG adducts that would cause more of a global change in DNA conformation. Provided it has favourable toxicity profile, TH1 has the potential to be developed into a highly active anticancer drug with a wider spectrum of activity than cisplatin.