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Lung cancer (LC) is a leading cause of global cancer-related deaths, highlighting the development of innovative methods for biomarker detection improving the early diagnostics. microRNAs (miRs) alterations are known to be involved in the initiation and progression of human cancers and can act as biomarkers for diagnostics and treatment. Herein, we develop the application of molecular beacon (MB) technology to monitor miR-155-3p expression in human lung adenocarcinoma A549 cells without complementary DNA synthesis, amplification, or expensive reagents. Furthermore, we produced gold nanoparticles (AuNPs) for delivering antisense oligonucleotides into A549 cells to reduce miR-155-3p expression, which was subsequently detectable using the MB. The MB was designed and structural characterized by Förster Resonance Energy Transfer (FRET)-melting, Circular Dichroism (CD), Nuclear magnetic resonance (NMR), and fluorometric experiments, and then the hybridization conditions were optimized for an in vitro approach involving the detection of miR-155-3p in total RNA extracted from A549 cell line. The expression profile of miR-155-3p was obtained by RT-qPCR. The results demonstrated that MB was properly designed and showed efficacy in targeting miR-155-3p. Furthermore, a limit of detection down to nanomolar concentration was achieved and the specificity of the biosensor was proved. Moreover, the self-assembly of ASOs with AuNPs exhibited exceptional target specificity, effectively silencing miR-155-3p. Notably, compared to lipid-based transfection agent, AuNPs displayed superior silencing efficiency. We highlighted the ability of MB to detect changes in the target gene expression after gene silencing. Overall, this innovative approach represents a promising tool for detecting various biomarkers at the same time, with potential applications in clinical settings. [Display omitted] • A novel MB probe has been designed for single-step miR-155-3p detection. • The assay showed promising sensitivity with a detection limit of 0.66 nM. • Effective application of antisense oligonucleotides vectorized by AuNPs for miR-155-3p silencing. • MB detects post-gene silencing alterations, enabling miR-155-3p expression monitoring. • Molecular beacon-based assay is fast, simple, and inexpensive. [ABSTRACT FROM AUTHOR]

Due to their small size and unique properties, multifunctional nanoparticles arise as versatile delivery systems easily grafted with a vast array of functional moieties, such as anticancer cytotoxic chemotherapeutics and targeting agents. Here, we formulated a multifunctional gold-nanoparticle (AuNP) system composed of a monoclonal antibody against epidermal growth factor receptor (EGFR) (anti-EGFR D-11) for active targeting and a Co(II) coordination compound [CoCl(H 2 O)(phendione) 2 ][BF 4 ] (phendione = 1,10-phenanthroline-5,6-dione) (TS265) with proven antiproliferative activity towards cancer cells (designated as TargetNanoTS265). The efficacy of this nanoformulation, and the non-targeted counterpart (NanoTS265), were evaluated in vitro using cancer cell models and in vivo using mice xenografts. Compared to the free compound, both nanoformulations (TargetNanoTS265 and NanoTS265) efficiently delivered the cytotoxic cargo in a controlled selective manner due to the active targeting, boosting tumor cytotoxicity. Treatment of HCT116-derived xenografts tumors with TargetNanoTS265 led to 93% tumor reduction. This simple conceptual nanoformulation demonstrates the potential of nanovectorization of chemotherapeutics via simple assembly onto AuNPs of BSA/HAS-drug conjugates that may easily be expanded to suit other cargo of novel compounds that require optimized controlled delivery to cancer target. [ABSTRACT FROM AUTHOR]

Two water soluble heterometallic potassium–dioxidovanadium polymers, [KVO 2 (L 1 )] n (1) and [KVO 2 (L 2 )(H 2 O)] n (2) [H 2 L 1 = (2,3-dihydroxybenzylidene)-2-hydroxybenzohydrazide and H 2 L 2 = (2,3-dihydroxybenzylidene)benzohydrazide], have been synthesized and characterized by IR, NMR, elemental analysis and single crystal X-ray diffraction. The antiproliferative potentials of 1 and 2 were examined towards human colorectal carcinoma (HCT116), and lung (A549) and breast (MCF7) adenocarcinoma cell lines. 1 exhibits a high cytotoxic activity against colorectal carcinoma cells (HCT116), with IC 50 lower than those for cisplatin. [ABSTRACT FROM AUTHOR]

• First report of helichrysum odoratissimum ethanolic extract (HO) against A549 lung cancer with an IC 50 of 83.43 ± 1.60 µg/mL. • HO inhibited COX-2 and 5-LOX with IC 50 values of 7.94 ± 3.84 µg/mL and 2.08 ± 1.35 µg/mL, respectively. • HO (at 125 µg/mL) significantly inhibited NAD(P)H quinone oxidoreductase 1 (NQO1) in A549 cells. • HO (at 18.5 µg/egg) showed a 31.65 ± 12.80 % inhibition of blood vessel formation in the ex ovo YSM assay. • Synthesised gold nanoparticle using the HO ethanolic extract indicated immunomodulatory potential via macrophage uptake. Lung cancer remains the top killing cancer worldwide despite advances in treatment. Seven ethanolic plant extracts were selected and evaluated for their antiproliferative activity against the two main types of lung cancers: non-small cell (A549) and small cell lung cancer cells (SHP-77). An ethanolic extract of Helichrysum odoratissimum Sweet (HO) showed significant antiproliferative activity against lung cancer, with a fifty percent inhibitory concentration (IC 50) of 83.43 ± 1.60 µg/mL (A549), 49.46 ± 0.48 µg/mL (SHP-77) and 50.71 ± 2.27 µg/mL, against normal lung epithelial cells (MRC-5), resulting in a selectivity index (SI) value of 0.61 on A549 cells and 1.03 on SHP-77 cells, which was compared to the positive drug control, actinomycin D where the SI values were found to be 2 and 0.25 against A549 and SHP-77 cells, respectively. Against murine macrophages (RAW 264.7) and hepatocytes (HepG2), the HO ethanolic extract showed IC 50 values of 60.15 ± 1.98 µg/mL and 23.61 ± 1.06 µg/mL, respectively. Microscopy showed that the HO ethanolic extract induced apoptosis in the A549 and HepG2 cells at 50 µg/mL and 300 µg/mL, respectively. The HO ethanolic extract, furthermore, inhibited the pro-inflammatory enzymes, cyclooxygenase 2 (COX-2) and 5-lipoxygenase (5-LOX) with IC 50 values of 7.94 ± 3.84 µg/mL and 2.08 ± 1.35 µg/mL, respectively, whereas the positive controls Ibuprofen (COX-2) and Zileuton (5-LOX) showed IC 50 values of 0.85 ± 0.14 µg/mL and 0.06 ± 0.05 µg/mL, respectively. The activity of NAD(P)H quinone oxidoreductase-1 (NQO1), which is a direct target of nuclear factor erythroid-2-related factor-2 (NRF2), was significantly inhibited in the A549 cells by the HO ethanolic extract (at 125 µg/mL) when compared to the positive control, brusatol (at 500 nM). Using the ex ovo yolk sac membrane (YSM) assay, the HO ethanolic extract (at 18.5 µg/egg) showed a 31.65 ± 12.80% inhibition of blood vessel formation. This is the first report of the noteworthy antiproliferative activity of the HO ethanolic extract on lung cancer cells including its potential to target several enzymes associated with inflammation and therefore, should be considered for further analysis. [ABSTRACT FROM AUTHOR]

The ruthenium arene fragment is a rich source for the design of anticancer drugs; in this design, the co-ligand is a critical factor for obtaining effective anticancer complexes. In comparison with other types of ligands, N -heterocyclic carbenes (NHCs) have been less explored, despite the versatility in structural modifications and the marked stabilization of metal ions, being these characteristics important for the design of metal drugs. However, notable advances have been made in the development of NHC Ruthenium arene as anticancer agents. These advances include high antitumor activities, proven both in in vitro and in in vivo models and, in some cases, with marked selectivity against tumorigenic cells. The versatility of the structure has played a fundamental role, since they have allowed a selective interaction with their molecular targets through, for example, bio-conjugation with known anticancer molecules. For this reason, the structure-activity relationship of the imidazole, benzimidazole, and abnormal NHC ruthenium (II) η 6-arene complexes have been studied. Taking into account this study, several synthetic aspects are provided to contribute to the next generations of this kind of complexes. Moreover, in recent years nanotechnology has provided innovative nanomedicines, where half-sandwich Ruthenium(II) complexes are paving their way. In this review, the recent developments in nanomaterials functionalized with Ruthenium complexes for targeted drug delivery to tumors will also be highlighted. The half-sandwich Ru(II) N -heterocyclic carbene complexes represent a promisor scaffold for anticancer drug discovery. [Display omitted] • Benzyl functionalization of wingtips, denticity of NHC ligand and counter-anions affect antitumor properties • Abnormal half-sandwich Ru(II) N -heterocyclic carbenes with long-chain alkyl and benzyl functionalization show great antitumor potential with low side-effects • Incorporation of half-sandwich Ru(II) NHC complexes in nanoformulations might improve targeting and delivery leading to a new class of innovative nanomedicines. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • mcl-PHA production by P. putida NRRL B-14785 is described for the first time. • P. putida and P. chlororaphis produced extracellular polymers together with mcl-PHA. • Extracellular polymers were found to be efficient bioemulsifiers. • Bioemulsifiers showed no cytotoxicity on normal skin primary cell lines. • Bioemulsifier by P. chlororaphis halved the growth rate of MNT-1 melanoma cells. Abstract While screening for polyhydroxyalkanoate (PHA) producing strains, using glycerol rich by-product as carbon source, it was observed that extracellular polymers were also secreted into the culture broth. The scope of this study was to characterize both intracellular and extracellular polymers, produced by Pseudomonas putida NRRL B-14875 and Pseudomonas chlororaphis DSM 50083, mostly focusing on those novel extracellular polymers. It was found that they fall into the class of bioemulsifiers (BE), as they showed excellent emulsion stability against different hydrocarbons/oils at various pH conditions, temperature and salinity concentrations. Cytotoxicity tests revealed that BE produced by P. chlororaphis inhibited the growth of highly pigmented human melanoma cells (MNT-1) by 50% at concentrations between 150 and 200 μg/mL, while no effect was observed on normal skin primary keratinocytes and melanocytes. This is the first study reporting mcl-PHA production by P. putida NRRL B-14785 and bioemulsifier production from both P. putida and P. chlororaphis strains. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract The major challenge of the pharmaceutical industry is to find potential solvents for poorly water-soluble drug molecules. Ionic liquids (ILs) have attracted this industry as (co-) solvents due to their unique physicochemical and biological properties. Herein, a straightforward approach for the enhancement of the water solubility of paracetamol and sodium diclofenac is presented, using new biocompatible N -acetyl amino acid N -alkyl cholinium-based ionic liquids as co-solvents (0.2–1 mol%). These new ionic liquids were able to increase the water solubility of these drugs up to four times that in pure water or in an inorganic salt solution. In the presence of these ILs, the drugs lipophilicity (log P was not significantly changed for paracetamol, but for sodium diclofenac it was possible to decrease significantly its lipophilicity. Concerning cytotoxicity in human dermal fibroblasts it was observed that ILs did not show a significant toxicity, and were able to improve cell viability compared with the respective precursors. [ABSTRACT FROM AUTHOR]

Sulfate-reducing bacteria (SRB) are a diverse group of anaerobic microorganisms that obtain their energy from dissimilatory sulfate reduction. Some SRB species have high respiratory versatility due to the possible use of alternative electron acceptors. A good example is Desulfovibrio desulfuricans ATCC 27774, which grows in the presence of nitrate (end product: ammonium) with higher rates and yields to those observed in sulfate containing medium (end product: sulfide). In this work, the mechanisms supporting the respiratory versatility of D . desulfuricans were unraveled through the analysis of the proteome of the bacterium under different experimental conditions. The most remarkable difference in the two-dimensional gel electrophoresis maps is the high number of spots exclusively represented in the nitrate medium. Most of the proteins with increase abundance are involved in the energy metabolism and the biosynthesis of amino acids (or proteins), especially those participating in ammonium assimilation processes. qPCR analysis performed during different stages of the bacterium's growth showed that the genes involved in nitrate and nitrite reduction ( napA and nrfA , respectively) have different expressions profiles: while napA did not vary significantly, nrfA was highly expressed at a 6 h time point. Nitrite levels measured along the growth curve revealed a peak at 3 h. Thus, the initial consumption of nitrate and concomitant production of nitrite must induce nrfA expression. The activation of alternative mechanisms for energy production, aside several N-assimilation metabolisms and detoxification processes, solves potential survival problems in adapting to different environments and contributes to higher bacterial growth rates. [ABSTRACT FROM AUTHOR]

In this work, biocompatible and biodegradable poly( d - l -lactide-co-glycolide) (PLGA) composite microparticles with potential use as carrier for vaccines and other drugs to the lungs were developed using supercritical CO 2 -assisted spray-drying (SASD). Bovine serum albumin (BSA) was chosen as model vaccine, and l -leucine as a dispersibility enhancer, and their effects on the particle characteristics were evaluated. The dry powder formulations (DPFs) were characterized in terms of their morphology and aerodynamic performance using an in vitro aerosolization study – Andersen cascade impactor (ACI) − to obtain data such as the fine particle fraction (FPF) with percentages up to 43.4%, and the mass median aerodynamic diameter (MMAD) values between the 1.7 and 3.5 μm. Additionally, pharmacokinetic and cytotoxicity studies were performed confirming that the produced particles have all the necessary requirements for potential pulmonary delivery. [ABSTRACT FROM AUTHOR]

A series of four mixed ligand aroylhydrazone and N-donor heterocyclic Lewis base Cu(II) complexes [CuL(X)] 2 [L refers to the dianionic form of (5-bromo-2-hydroxybenzylidene)-2-hydroxybenzohydrazide; X = pyrazine (Pz; 1 ), pyridine (Py; 2 ), imidazole (Imz; 3 ) and 3-pyridinecarbonitrile (3-PyCN; 4 )] has been synthesized and characterized by elemental analysis, various spectroscopic techniques and X-ray crystallography (for 1 , 2 and 4 ). The antiproliferative effect of complexes 1–4 was examined in 4 human tumor cell lines (ovarian carcinoma (A2780), colorectal carcinoma (HCT116), lung adenocarcinoma (A549) and breast adenocarcinoma (MCF7)) and in normal human primary Fibroblasts. Complex 4 exhibits a high cytotoxic activity against ovarian and colorectal carcinoma cells (A2780, HCT116 respectively), with IC 50 much lower than those for normal primary fibroblasts. Complex 4 could induce cell death via apoptosis but not autophagy in colorectal carcinoma cells. [ABSTRACT FROM AUTHOR]

Streptococcus dysgalactiae subsp. dysgalactiae (SDSD) are considered exclusive animal pathogens; however, a putative zoonotic upper limb cellulitis, a prosthetic joint infection and an infective endocarditis were described in humans. To unravel if bovine SDSD isolates are able to infect human cells, the adherence and internalization to human primary keratinocytes of two bovine SDSD strains isolated from milk collected from udder were analyzed. Bacterial adhesion assays and confocal microscopy indicate a high adherence and internalization of SDSD isolates to human cells, suggesting for the first time the ability of bovine isolates to infect human cells. [ABSTRACT FROM AUTHOR]

The characterization of the antiproliferative potential of the ketoimine platinum complex trans -[PtCl 2 {RC( O)N CN–(H)C(Me) 2 –CH 2 CH 2 } 2 ] (R = CH 2 CO 2 Me) is reported. It showed a higher cytotoxicity against HCT116 and HepG2 cancer cells (IC 50 values of 22.74 ± 0.04 μM and 22.08 ± 0.08 μM, respectively) compared to fibroblasts and a non-tumorigenic cell line. It was also observed a moderate ability of the complex to induce apoptosis in HCT116 cells, as observed by fluorescence microscopy and flow cytometry. The observed antiproliferative activities of the complex are mostly due to delay in the cell cycle progression. In vitro DNA interaction studies revealed a DNA affinity constant of 6.67 × 10 5 M −1 , suggesting a high affinity to DNA, by comparison to the value obtained for doxorubicin. A decrease in the electrophoretic mobility of the supercoiled plasmid DNA (pDNA) suggested the formation of complex-DNA adducts. However, the complex did not exhibit relevant genotoxicity in V79 cells. Proteomic assays demonstrated that the ketoimine Pt(II) complex promotes an overexpression of two negative cell cycle regulators, PA2G4 and 14-3-3σ, and PHB, and a decrease in expression of VDAC1 and HSP90B, probably associated with the antiproliferative potential. The ketoimine Pt(II) complex is able to trigger an overexpression of cytoskeleton-associated proteins in agreement with its ability to maintain cell structure, and an overexpression of oxidative stress enzymes, coping with the induction of ROS formation, observed by in vitro EMSA assays. In conclusion, the ketoimine Pt(II) complex is an antiproliferative agent with potential to be used against cancer cells. [ABSTRACT FROM AUTHOR]

Two organotin(IV) complexes, [Sn(C6H5)3HL1] (1) and [Sn(C2H5)2(1κO,2κO-H3L2)(1κO 2-H3L2)(μ3-O)]2 (2), were isolated upon interaction of Ph3SnCl and Et2SnO with 2-(2-(2,4-dioxopentan-3-ylidene)hydrazinyl)benzoic acid (H2L1) and 2-(2-(2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene) hydrazinyl)benzoic acid (H4L2), respectively, in toluene solution. Complexes 1 and 2 were characterized by IR and NMR spectroscopies, elemental and single crystal X-ray diffraction analyses. While in 1 the (HL1)– ligand binds the metal in a chelating bidentate mode, in 2 the (H3L2)– anion acts not only as a chelating bidentate but also as a bridging bidentate donor. The in vitro antiproliferative activity against human colorectal carcinoma (HCT116) and human hepatocellular carcinoma (HEPG2) cells lines demonstrated that compound 1 possesses high in vitro antiproliferative activity with IC50 values of 0.0284 ± 0.0001 μM and 0.287 ± 0.0001 μM for HCT116 and HEPG2 cells, respectively. [ABSTRACT FROM AUTHOR]

Cancer is the second leading cause of death worldwide. Cisplatin has challenged cancer treatment; however, resistance and side effects hamper its use. New agents displaying improved activity and more reduced side effects relative to cisplatin are needed. In this work we present the synthesis, characterization and biological activities of three complexes with quinoline-substituted 2,2′:6′,2″-terpyridine ligand: [Pt(4′-(2-quin)-terpy)Cl](SO 3 CF 3) (1), [Au(4′-(2-quin)-terpy)Cl](PF 6) 2 ·CH 3 CN (2) and [Cu(4′-(2-quin)-terpy)Cl](PF 6) (3). The three complexes displayed a high antiproliferative activity in ovarian carcinoma cell line (A2780) and even more noticeable in a colorectal carcinoma cell line (HCT116) following the order 3 > 2 > 1. The complexes IC 50 are at least 20 × lower than the IC 50 displayed by cisplatin (15.4 μM) in HCT116 cell line while displaying at the same time, much reduced cytotoxicity in a normal dermal fibroblast culture. These cytotoxic activities seem to be correlated with the inclination angles of 2-quin unit to the central pyridine. Interestingly, all complexes can interact with calf-thymus DNA (CT-DNA) in vitro via different mechanisms, although intercalation seems to be the preferred mechanism at least for 2 and 3 at higher concentrations of DNA. Moreover, circular dichroism (CD) data seems to indicate that complex 3 , more planar, induces a high destabilization of the DNA double helix (shift from B-form to Z-form). Higher the deviation from planar, the lower the cytotoxicity displayed by the complexes. Cellular uptake may be also responsible for the different cytotoxicity exhibited by complexes with 3 > 2 > 1. Complex 2 seems to enter cells more passively while complex 1 and 3 might enter cells via energy-dependent and -independent mechanisms. Complexes 1 – 3 were shown to induce ROS are associated with the increased apoptosis and autophagy. Moreover, all complexes dissipate the mitochondrial membrane potential leading to an increased BAX/BCL-2 ratio that triggered apoptosis. Complexes 2 and 3 were also shown to exhibit an anti-angiogenic effect by significantly reduce the number of newly formed blood vessel in a CAM model with no toxicity in this in vivo model. Our results seem to suggest that the increased cytotoxicity of complex 3 in HCT116 cells and its potential interest for further translation to pre-clinical mice xenografts might be associated with: 1) higher % of internalization of HCT116 cells via energy-dependent and -independent mechanisms; 2) ability to intercalate DNA and due to its planarity induced higher destabilization of DNA; 3) induce intracellular ROS that trigger apoptosis and autophagy; 4) low toxicity in an in vivo model of CAM; 5) potential anti-angiogenic effect. [Display omitted] • Pt(II), Au(III), Cu(II) complexes of 4′-(2-quinolinyl)-terpyridine were studied. • Their high antiproliferative activity in A2780 and HCT116 cell lines was confirmed. • Complexes' cytotoxic activity was correlated with inclination of 2-quinolinyl unit. • Induction of apoptosis and autophagy was due to ROS production. • Anti-angiogenic potential of two complexes without toxicity in an in vivo CAM assay. [ABSTRACT FROM AUTHOR]

Edible flowers are being used as a new ingredient in modern gastronomy. Recently, these products have also gained interest as an important source of phenolic compounds with potential for biomedical applications. The present work studied a methanolic extract of Rosa x hybrida in which 35 individual phenolic compounds were identified. The extract has been evaluated for its antiproliferative properties in ovarian carcinoma cells. Results showed that the antiproliferative effect was associated with the induction of autophagy and apoptosis with the concomitant ROS increase probably related to mitochondria dysfunction. These antiproliferative effects might be associated with some components of the extract such as quercetin. The extract did not induce damage in healthy cells and that it was able to improve the wound healing activity. The present study also evaluated the properties of the mentioned extract in vivo in C. elegans. Tests demonstrated a lack of toxicity in the worm model. Promising results have been obtained in transgenic strains of C. elegans that produce human beta amyloid peptide, suggesting the possible utility of the extract from the point of view of Alzheimer disease. Altogether, results suggest that Rosa x hybrida extracts could be a new tool for the development of functional foods. Image 1 • Rosa x hybrida extract inhibited the growth of ovarian tumoral cell lines. • The antitumoral effect was mediated by induction of autophagy and ROS production. • Petals extract was not toxic for fibroblasts and worms. • The extract might be useful for beta-amyloid reduction in Alzheimer disease. [ABSTRACT FROM AUTHOR]

Cancer is still one of the deadliest diseases worldwide despite the efforts in its early detection and treatment strategies. However, most chemotherapeutic agents still present side effects in normal tissues and acquired resistance that limit their efficacy. Spiropyrazoline oxindoles might be good alternatives as they have shown antiproliferative activity in human breast and colon cancer cell lines, without eliciting cytotoxicity in healthy cells. However, their potential for ovarian cancer was never tested. In this work, the antiproliferative activity of five spiropyrazoline oxindoles was assessed in ovarian cancer cells A2780 and the biological targets and mechanism of action of the most promising compound evaluated. Compound 1a showed the highest antiproliferative effect, as well as the highest selectivity for A2780 cells compared to healthy fibroblasts. This antiproliferative effect results from the induction of cell death by mitochondria-mediated apoptosis and autophagy. In vitro DNA interaction studies demonstrated that 1a interacts with DNA by groove-binding, without triggering genotoxicity. In addition, 1a showed a strong affinity to bovine serum albumin that might be important for further inclusion in drug delivery platforms. Proteomic studies reinforced 1a role in promoting A2780 endoplasmatic reticulum (ER) stress by destabilizing the correct protein folding which triggers cell death via apoptosis and autophagy. [ABSTRACT FROM AUTHOR]

A 'scorpionate' type precursor bdtbpza = bis(3,5-di- t -butylpyrazol-1-yl)acetate] has been employed to synthesize two mononuclear ZnII and CoII derivatives, namely [Zn(bdtbpza) 2 (H 2 O) 2 ·2.5CH 3 OH·2[(CH 3) 3 C-C 3 H 2 N 2 -C(CH 3) 3 (1) and [Co(bdtbpza) 2 (CH 3 OH) 4 (2) in good yield. Single crystal X-ray diffraction analysis reveals that in 1 , the ZnII atom is tetrahedrally surrounded by a pair of O acetate atoms of two bis(pyrazol-1-yl)acetate units and two water molecules; while in 2 , the CoII atom shows an octahedral environment coordinating a pair of O acetate atoms of two bis(pyrazol-1-yl)acetate units along with four methanol molecules. The EPR spectra of 2 recorded at 77 and 298 K confirmed the tetragonal symmetry of the high spin Co(II). The DFT (Density functional theory) computation is in good agreement with the geometry proposed for compounds 1 and 2. Both the compounds display a high antiproliferative activity against HCT116 (colorectal carcinoma) and A2780 (ovarian carcinoma) cell lines compared to human normal dermal fibroblasts. In the case of A2780 cells, compounds 1 and 2 exhibit IC 50 values that are similar to those described for cisplatin, a widely used chemotherapeutic drug. Exposure of A2780 cells to the IC 50 concentration of each compound led to an increase of the number of apoptotic and autophagic cells. In the case of compound 1 , the accumulation of intracellular ROS (Reactive oxygen species) is responsible for triggering A2780 cell death. Two mononuclear Zn(II) and Co(II) derivatives incorporating 'scorpionate' precursor are afforded and characterized by solid state X-ray diffractometry, spectral and DFT (Density functional theory) studies. The cytotoxic evaluation and anti-proliferative activity alongwith autophagy on human cancer cell lines for both derivatives are discussed. Unlabelled Image • Two octahedral ZnII and CoII complexes with a 'scorpionate' ligand were synthesized. • The complexes were characterized by X-ray, IR, EPR and density function theory. • Antiproliferative activity of both complexes on human cancer cell lines are reported. • Both autophagy and apoptosis may furnish to the reduction of cell viability in A2780 cells. • The Zn(II) complex induces oxidative damages leading to ROS accumulation. [ABSTRACT FROM AUTHOR]

The syntheses of the heterometallic sodium and potassium-dioxidovanadium 2D polymers, [NaVO 2 (1κN OO' ;2κ O"- L)(H 2 O)] n (1) and [KVO 2 (1κN OO' ;2κ O' ;3κ O"- L)(EtOH)] n (2) (where the κ notation indicates the coordinating atoms of the polydentate ligand L) derived from (3,5-di- tert -butyl-2-hydroxybenzylidene)-2-hydroxybenzohydrazide (H 2 L) are reported. The polymers were characterized by IR, NMR, elemental analysis and single crystal X-ray diffraction analysis. The antiproliferative potential of 1 and 2 was examined towards four human cancer cell lines (ovarian carcinoma, A2780, colorectal carcinoma, HCT116, prostate carcinoma, PC3 and breast adenocarcinoma, MCF-7cell lines) and normal human fibroblasts. Complex 1 and 2 showed the highest cytotoxic activity against A2780 cell line (IC 50 8.2 and 11.3 μM, respectively) with 1 > 2 and an IC 50 in the same range as cisplatin (IC 50 3.4 μM; obtained in the same experimental conditions) but, interestingly, with no cytotoxicity to healthy human fibroblasts for concentrations up to 75 μM. This high cytotoxicity of 1 in ovarian cancer cells and its low cytotoxicity in healthy cells demonstrates its potential for further biological studies. Our results suggest that both complexes induce ovarian carcinoma cell death via apoptosis and autophagy, but autophagy is the main biological cause of the reduction of viability observed and that ROS (reactive oxygen species) may play an important role in triggering cell death. The antiproliferative potential of heterometallic sodium and potassium-dioxidovanadium 2D polymers derived from aroylhydrazone ligand was examined towards A2780, a human ovarian carcinoma cell line. The sodium-dioxidovanadium polymer exhibits high cytotoxicity towards ovarian cancer cells. Unlabelled Image • Syntheses of heterometallic sodium or potassium-dioxidovanadium polymers • They are characterized by single crystal X-ray diffraction analysis. • Antiproliferative potential towards A2780 cell line was examined. • Sodium-dioxidovanadium polymer exhibits high cytotoxicity. [ABSTRACT FROM AUTHOR]

The water-soluble 1D helical coordination polymer [Ag(Tpms)] n (1) [Tpms = tris(pyrazolyl)methane sulfonate, −O 3 SC(pz) 3 ; pz = pyrazolyl] was synthesized and fully characterized, its single-crystal X-ray diffraction analysis revealing the ligand acting as a bridging chelate N 3 -donor ligand. The antiproliferative potential of 1 was performed on two human tumour cell lines, A2780 and HCT116, and in normal fibroblasts, with a much higher effect in the former cell line (IC 50 of 0.04 μM) as compared to the latter cell line and to normal fibroblasts. Compound 1 does not alter cell cycle progression but interferes with the adherence of A2780 cells triggering cell apoptosis. Apoptosis appears to occur via the extrinsic pathway (no changes in mitochondria membrane potential, reactive oxygen species (ROS) and pro-apoptotic (B-cell lymphoma 2 (BCL-2) associated protein (BAX))/anti-apoptotic (BCL-2) ratio) being this hypothesis also supported by the presence of silver mainly in the supernatants of A2780 cells. Results also indicated that cell death via autophagy was triggered. Proteomic analysis allowed us to confirm that compound 1 is able to induce a stress response in A2780 cells that is related with its antiproliferative activity and the trigger of apoptosis. The polymer [Ag(tris(pyrazolyl)methane sulfonate)]n was synthesized and characterized. A cytotoxicity analysis revealed higher antiproliferative effect against ovarian carcinoma compared to normal fibroblasts. The biological effect was evaluated in terms of cell adhesion, apoptosis induction, effect on the cell cycle, reactive oxygen species generation, internalization of the complex and proteomic analysis. Unlabelled Image • [Ag(tris(pyrazolyl)methane sulfonate)]n was synthesized and characterized. • X-ray analysis revealed tris(pyrazolyl)methane sulfonate as bridging chelate N3-donor. • The antiproliferative potential of the polymer was characterized. • The polymer shows higher antiproliferative effect in ovarian carcinoma than non-tumour cells. • Antiproliferative effect is due to apoptosis, autophagy and loss of cell adhesion. [ABSTRACT FROM AUTHOR]