Search

One of the modern approaches to the treatment of cancer is the creation of targeted delivery systems for anticancer drugs, which allows increasing the concentration of the delivered substance in the right place and preventing its accumulation in healthy organs and tissues. At the same time, one can also expect an increase in the duration and effectiveness of the drugs, as well as a reduction in side effects during therapy. The hyaluronic acid receptor CD44, which, according to the literature, is highly expressed in many types of tumors and regulates metastasis, is a promising target for targeted delivery of anticancer drugs. The purpose of this study was to evaluate the effect of a supramolecular delivery system based on hyaluronic acid with nanosized cavitand cyclodextrin on the antitumor properties of oxaliplatin in vitro. Cell lines 1301, SK-MEL-28 and B16 were used as tumor cells. Cells were cultured in the presence of a delivery system based on hyaluronic acid (HACD), oxaliplatin (OX), and their complex (HACD-OX) at various concentrations in complete culture medium RPMI-1640 containing 0.3% L-glutamine, 4% gentamicin and 10% inactivated FBS serum for 48 hours in a humidified atmosphere of 5% CO2 at 37°C. The effect of the studied compounds on the viability of cell cultures was assessed using the WST test. It was shown that in the case of the T-cell lymphoma cell line 1301, the HACD delivery system did not affect the ability of OX to reduce the viability of tumor cells of this line; the effect of free oxaliplatin and the complex was comparable. However, in the case of melanoma cells (B16 and SK-MEL-28), the HACD-DOX complex has a more pronounced antitumor effect, causing a statistically significant decrease in the viability of B16 and SK-MEL-28 cells compared to free oxaliplatin.

Background and Aim: Sorafenib and sunitinib are tyrosine kinase receptor inhibitors commonly used in chemotherapy. This study aimed to compare the effects of simultaneous treatment with these two anti-tumor drugs on breast (MDA-MB-231) and pancreatic (Panc1) cancer cell lines. Methods: In this experimental study, breast cancer (MDA-MB-231) and pancreatic cancer (Panc1) cell lines were cultured. The cells were then treated simultaneously with sorafenib and sunitinib for 48 hours. Cell viability was assessed using the MTT assay, while cell migration was evaluated using the Scratch assay. Results: The IC50 values for both anticancer drugs, sorafenib and sunitinib, were higher in the pancreatic cell line (Panc1) compared to the breast cell line (MDA-MB-231). The simultaneous treatment with these two drugs was more effective in reducing the viability and migration of breast cancer cells (MDA-MB-231) than in pancreatic cancer cells (Panc1). Furthermore, morphological changes indicative of cancer cell damage were observed more frequently in the breast cell line (MDA-MB-231) following simultaneous treatment with both drugs. Conclusion: The simultaneous treatment with the tyrosine kinase receptor inhibitors sorafenib and sunitinib was more effective in inhibiting the viability and migration of breast cancer cells (MDA-MB-231). This increased effectiveness may be attributed to the higher expression of tyrosine kinase receptors in breast cancer. However, further experiments are necessary to elucidate the molecular mechanisms underlying these effects.

Grafted copolymers of chitosan–vinylpyrrolidone, water-soluble at a pH of 6.8–7.5, were obtained. A technique has been developed for obtaining an aggregatively stable system of platinum nanoparticles in copolymer solutions with an average size of ~4 nm. The thermophysical and structural characteristics of the powdered composition of a platinum nanoparticle-copolymer are investigated. An in vitro comparison of the antitumor activity of solutions of the developed composition and cisplatin at the same platinum concentration was performed. It was found that with respect to the culture of HeLa Kyoto and A431 cancer cells, the composition is five and two times less effective than cisplatin, respectively. Along with this, the biocompatibility of the composition is 17 times higher than that of cisplatin, which allows its use at elevated concentrations and the development of an antitumor agent with platinum nanoparticles commensurate in effectiveness with cisplatin. [ABSTRACT FROM AUTHOR]

The therapeutic effects of curcumin and its derivatives, based on research in recent years, are limited by their low bioavailability. To improve bioavailability and develop the medical field of application, different delivery systems have been developed that are adapted to certain environments or the proposed target type. This study presents some half-curcuminoids prepared by the condensation of acetylacetone with 4-hydroxybenzaldehyde (C1), 4-hydroxy-3-methoxybenzaldehyde (C2), 4-acetamidobenzaldehyde (C3), or 4-diethylaminobenzaldehyde (C4), at microwaves as a simple, solvent-free, and eco-friendly method. The four compounds obtained were characterized in terms of morphostructural and photophysical properties. Following the predictions of theoretical studies on the biological activities related to the molecular structure, in vitro tests were performed for compounds C1–C3 to evaluate the antitumor properties and for C4's possible applications in the treatment of neurological diseases. The four compounds were encapsulated in two types of hydrogel matrices. First, the alginate–glucosamine network was generated and then the curcumin analogs were loaded (G1, G3, G5–G7, and G9). The second type of hydrogels was obtained by loading the active compound together with the generation of the hydrogel carrier matrices, by simply dissolving (G4 and G10) or by chemically binding half-curcuminoid derivatives to glucosamine (G2 and G8). Thus, two types of curcumin analog delivery systems were obtained, which could be applied in various types of medical treatments. [ABSTRACT FROM AUTHOR]

Extensive research into platinum-based chemotherapeutics has been underway for decades with ruthenium-based complexes emerging as interesting and potent candidates. Even still, there is no evidence of a single mechanism of action across all synthesized and tested Ru-based complexes, prompting the continuance of research in this field. In addition, the mechanism of action varies according to cell line and/or animal model and is seemingly highly individualized and personalized. In accordance with this, the ruthenium complexes are able to activate specific molecular pathways and interact with certain targets within the cell, sometimes reported simultaneously. In this review, we attempt to give a new perspective on ruthenium complexes’ anti-cancer properties and organize selected results from the past 15 years of research connecting their structure with the reported mechanism of action. These results corroborate the previously reported great potential that ruthenium complexes have on cancer in vitro. In addition, the review provides insight into Ru drugs in their clinical trials and their efficacy against cancer including a historical context on metallodrugs, particularly platinum-based complexes, and their antitumor capability.

The therapeutic effects of curcumin and its derivatives, based on research in recent years, are limited by their low bioavailability. To improve bioavailability and develop the medical field of application, different delivery systems have been developed that are adapted to certain environments or the proposed target type. This study presents some half-curcuminoids prepared by the condensation of acetylacetone with 4-hydroxybenzaldehyde (C1), 4-hydroxy-3-methoxybenzaldehyde (C2), 4-acetamidobenzaldehyde (C3), or 4-diethylaminobenzaldehyde (C4), at microwaves as a simple, solvent-free, and eco-friendly method. The four compounds obtained were characterized in terms of morphostructural and photophysical properties. Following the predictions of theoretical studies on the biological activities related to the molecular structure, in vitro tests were performed for compounds C1–C3 to evaluate the antitumor properties and for C4’s possible applications in the treatment of neurological diseases. The four compounds were encapsulated in two types of hydrogel matrices. First, the alginate–glucosamine network was generated and then the curcumin analogs were loaded (G1, G3, G5–G7, and G9). The second type of hydrogels was obtained by loading the active compound together with the generation of the hydrogel carrier matrices, by simply dissolving (G4 and G10) or by chemically binding half-curcuminoid derivatives to glucosamine (G2 and G8). Thus, two types of curcumin analog delivery systems were obtained, which could be applied in various types of medical treatments.

In this review article, we embark on a thorough exploration of cannabinoids, compounds that have garnered considerable attention for their potential therapeutic applications. Initially, this article delves into the fundamental background of cannabinoids, emphasizing the role of endogenous cannabinoids in the human body and outlining their significance in studying neurodegenerative diseases and cancer. Building on this foundation, this article categorizes cannabinoids into three main types: phytocannabinoids (plant-derived cannabinoids), endocannabinoids (naturally occurring in the body), and synthetic cannabinoids (laboratory-produced cannabinoids). The intricate mechanisms through which these compounds interact with cannabinoid receptors and signaling pathways are elucidated. A comprehensive overview of cannabinoid pharmacology follows, highlighting their absorption, distribution, metabolism, and excretion, as well as their pharmacokinetic and pharmacodynamic properties. Special emphasis is placed on the role of cannabinoids in neurodegenerative diseases, showcasing their potential benefits in conditions such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis. The potential antitumor properties of cannabinoids are also investigated, exploring their potential therapeutic applications in cancer treatment and the mechanisms underlying their anticancer effects. Clinical aspects are thoroughly discussed, from the viability of cannabinoids as therapeutic agents to current clinical trials, safety considerations, and the adverse effects observed. This review culminates in a discussion of promising future research avenues and the broader implications for cannabinoid-based therapies, concluding with a reflection on the immense potential of cannabinoids in modern medicine. [ABSTRACT FROM AUTHOR]

To deliver therapeutic proteins into a living body, it is important to maintain their target activity in the gastrointestinal tract after oral administration. Secreted ribonuclease from Bacillus pumilus (binase) has antitumor and antiviral activity, which makes it a promising therapeutic agent. This globular protein of small molecular weight (12.2 kDa) is considered as a potential agent that induces apoptosis of tumor cells expressing certain oncogenes, including colorectal and duodenum cancer. The most important problem of its usage is the preservation of its structure and target activity, which could be lost during oral administration. Here, we developed alginate microspheres reinforced with divalent cations and analyzed the enzyme release from them. Using methods of scanning electron microscopy, measurements of fluorescence, enzyme catalytic activity, and determination of viability of the duodenum adenocarcinoma tumor cell line, we characterized obtained microspheres and chose calcium as a biogenic ion-strengthening microsphere structure. Among such modified additivities as beta-casein, gelatin, and carbon nanotubes introduced into microspheres, only gelatin showed a pronounced increase in their stability and provided data on the prolonged action of enzyme release from microspheres into tumor cell culture medium during 48 h in an amount of about 70% of the loaded quantity. [ABSTRACT FROM AUTHOR]

To preserve the species diversity of Rhaponticum carthamoides, a Red Book plant that is a promising source of antitumor metabolites, it is important to grow cell cultures in vitro. The aim of the work is to select the optimal nutrient medium for growing suspension cells of Rhaponticum carthamoides, varying the mineral composition of the nutrient medium and growth regulators. To obtain suspension cells in vitro, nutrient media of various mineral compositions (Murashige–Skoog, Gamborg, and Schenk–Hildebrandt) and growth regulators (auxin: 3-indoleacetic acid (IAA); cytokinin: kinetin) were used. Cultivation parameters were as follows: 26°C, 60–70% humidity, 16-h daylight period and 21-day subculture cycle. For the obtained cell cultures, the viability, growth index, and specific growth rate were assessed. The results showed that the highest values of the studied parameters were observed when growing suspension cells on a nutrient medium with a Schenck–Hildebrandt mineral composition (SH) (77–82% viability of suspension cells, 6.11‒7.14 growth index, 0.17–0.21 day–1 specific growth rate). Methanol extracts were prepared from selected and prelyophilized cell samples and analyzed by high performance liquid chromatography. The results showed that suspension cultures (the best indicators were observed in sample no. 12 grown on SH medium supplemented with IAA and kinetin), as well as the control sample (methanol extract of crushed plant root), contained sitosterol (0.26 ± 0.01 mg/g in control; 1.54 ± 0.02 mg/g in no. 12), isofraxidine (1.15 ± 0.02 mg/g in control; 3.10 ± 0.04 mg/g in no. 12), chlorogenic (44.54 ± 0.14 mg/g in control; 66.87 ± 0.02 mg/g in no. 12), and coffee (50.15 ± 0.03 mg/g in control; 54.73 ± 0.06 mg/g in no. 12) acid. The extracts of suspension cultures (100 mg/mL) exhibited antitumor properties: a cytotoxic effect on tumor cells (PANC-1, LBR2, MDAMB-231, NT-29). Cell cultures grown on SH medium supplemented with IAA and kinetin exhibited the most pronounced antitumor properties since they contained a greater amount of biologically active substances in their composition. When the extract of sample no. 12 was added, the decrease in the viability of tumor cells was achieved by 40.57–53.23%. In the course of the work, the composition of the nutrient medium was selected, which allows one to grow the biomass of suspension cultures of Rhaponticum carthamoides cells, which exhibits antitumor properties. [ABSTRACT FROM AUTHOR]

Sabrina Bimonte, Marco Cascella Division of Anesthesia and Pain Medicine, Istituto Nazionale Tumori – IRCCS – “Fondazione G. Pascale, Naples, ItalyCorrespondence: Sabrina Bimonte Email s.bimonte@istitutotumori.na.itAbstract: Ovarian cancer represents the principal leading cause of women dying in the world. The first standard of care involved surgical resection followed by chemotherapy with taxane and platinum, mainly connected with cytotoxic chemotherapies causing diverse severe side effects. Unfortunately, recurrence represents a significant problem, and finally, patients develop resistance to cytotoxic chemotherapy. Other alternative treatments had been developed so far to reduce side effects; however, the outcomes are yet not empowering. Current shreds of evidence showed that epigallocatechin-3-gallate (EGCG) possesses an anticancer effect on ovarian carcinoma, mainly through the inhibition of different genetic signaling pathways which are closely linked with tumorigenesis. This review recapitulates these findings and highlights the roles of EGCG for the chemoprevention and treatment of ovarian cancer.Keywords: epigallocatechin-3-gallate, EGCG, ovarian cancer, antitumor properties, chemoprevention

Leukemia, as a part of hemoblastosises, is a malignant blood system disease, which is characterized by bone marrow damage, caused by leukemic stem cells, which appear due to disruption of self-renewal and differentiation of hempoetic stem cells and predecessor cells. In their turn, hemoblastoses are divided into two groups: bone marrow (acute leukemia, chronical leukemia, paraproteinemic hemoblastoses) and outside bone marrow (lymphogranulomatosis, or Hodgkin lymphoma, and non-Hodgkin malignant mymphomas). Nowadays in Ukraine, different kinds of leukemia are cured by various drugs, which have many side effects. Increase in effectivity of chemotherapy of tumor disease is primarily related to creation of new antitumor drugs of selective action. Which is why search for biologically active compounds with antitumor activity is a perspective direction in creation of new drugs. Aim of this work was synthesis of compounds with potential antitumor properties in a variety of [4-(41-chlorophenyl)-5,6,7,8-tetrahydro-2,2a,8a-triazacyclopenta[c,d]-azulen-1-yl-methyl]-para-tolylamin derivatives. As the objects of our studies, we have picked the derivatives of [4-(41-chlorophenyl)-5,6,7,8-tetrahydro-2,2а,8а-triazacyclopenta[c,d]-azulen-1-yl-methyl]-para-tolilamin (8 and 10 a, b). [4-(41-Chlorphenyl)-5,6,7,8-tetrahydro-2,2а,8а-triazacyclopenta[c,d]azulen-1-yl-methyl]-para-tolylamin (8) was obtained by boiling of equimolar quantities of 3-(41-methylphenyl)aminomethyl-6,7,8,9-tetrahydro-5Н-[1,2,4]triazolo[4,3-a]azepin (5) and α-brom-4-chloracetophenon in ethylacetate. Thioamides (10 a, b) were obtained by interaction of amin (8) with corresponding arylisothiocyanates (9 а, b) in dry benzene. Antitumor activity of [4-(41-chlorphenyl)-5,6,7,8-tetrahydro-2,2а,8а-triazacyclopenta[c,d]azulen-1-yl-methyl]-para-tolylamin (8) was studied in National Cancer Institute of Health, USA within Development Therapeutic Program. In experimental conditions [4-(41-chlorphenyl)-5,6,7,8-tetrahydro-2,2а,8а-triazacyclopenta[c,d]azulen-1-yl-methyl]-para-tolylamin (8) showed ability to inhibit growth of cancerous leukemia cells of CCRF-CEM, HL-60(TB), K-562, MOLT-4, RPMI-8226 and SR lines, higher than standard – 5-fluorouracil. Towards HL-60(TB) cells [4-(41-chlorphenyl)-5,6,7,8-tetrahydro-2,2а,8а- triazacyclopenta[c,d]azulen-1-yl-methyl]-para-tolylamin exceeds standard in effectivity by 64.68%. For K-562, MOLT-4, RPMI-8226 and SR cells, those numbers are equal to: 85.88%, 84.95%, 42.10% and 36.82% correspondingly. Towards CCRF-CEM cells, this compound not only inhibits cell growth and division, but also destroys them by 20.34%. Thus conducted studies confirm perceptivity of search for compounds with antitumor action on the basis of [4-(41-chlorophenyl)-5,6,7,8-tetrahydro-2,2а,8а-triazacyclopenta[c,d]azulen-1-yl­methyl]-para-tolylamin.

Ophiocordyceps sinensis and Cordyceps militaris metabolites showed a high potential in the treatment of tumors as well as some other diseases. Antitumor properties of O.sinensis and C.militaris submerged mycelium were investigated. It was found that the O.sinensis dry biomass in a dose of 50 mg/kg administered once a day to the mice with subcutaneously inoculated P388 lymp-holeucosis lowered the tumor growth by 65% vs. 54% for the C.militaris dry biomass. The water extract of O.sinensis submerged culture however accelerated the growth of the Р388 lympholeucosis tumor node in the mice almost two times, compared to the control. A greater caution in using this fungus as a source of biologically active substances is required since unwanted tumor-stimulating effects can arise.

Bauhinia scandens, an ornamental climbing vine, recently introduced in Brazil, in 2006 which has been gaining prominence due to its anti-tumor medicinal properties. A common feature amongst species of the Fabaceae family is dormancy due to the impermeability of the integument of the seed to water. The demand for seedlings of this species makes it necessary to elucidate the germination process and initial seedling growth. The objective of this study was to determine a method to overcome dormancy, thereby promoting seed germination and initial growth of B. scandens seedlings. The seeds were subjected to one of four treatments, besides the control: mechanical scarification, immersion in water (26 °C for 24 hours), immersion in hot water (86 °C for 24 hours, then 26 °C) and immersion in H2SO4 (95%) for 15, 30, 45, and 60 minutes. The seeds were evaluated for water content, germination (normal, abnormal seedlings, dormant and dead seeds), first count, mean germination time and relative frequency of germination. The seedlings were evaluated for emergence in sand, first count, emergence speed index, length and dry matter mass. B. scandens seeds should be immersed in H2SO4 for 45 and 60 minutes before sowing to overcome dormancy, in order to promote and standardize seed germination and enhance initial growth of the seedlings.

The dataset depicted in this article related to our earlier article entitled “Phytofabrication and encapsulated of silver nanoparticles from Gloriosa Superba” (Saradha Devi et al., 2017) [1], which reports the characteristic features (UV Visible spectra, FTIR, SEM, TEM, DLS, Zeta potential and XRD analysis) of the Gloriosa superba biosynthesised silver nanoparticles (AgNPs). In this context, the present dataset was provided to identify the antioxidant, antitumor and apoptotic (in DLA cells) properties with the synthesized AgNPs. The result enlightens the AgNPs exhibits antitumor, apoptotic activity in DLA cells and antioxidant properties. The results of the in vivo experiments increased life span of liver cells in DLA induced tumour mice and not showed any histopathological variations between control and DLA induced mice animals. The HPTLC examination of the Gloriosa superba (L.) seed extract infers the presence of colchicines derivatives as a major alkaloid sources.

Extensive research has been conducted on Camellia oleifera Abel., a cultivar predominantly distributed in China, to investigate its phytochemical composition, owning to its potential as an edible oil crop. Pentacyclic triterpene saponins, as essential active constituents, play a significant role in contributing to the pharmacological effects of this cultivar. The saponins derived from C. oleifera (CoS) offer a diverse array of bioactivity benefits, including antineoplastic/bactericidal/inflammatory properties, cardiovascular protection, neuroprotection, as well as hypoglycemic and hypolipidemic effects. This review presents a comprehensive analysis of the isolation and pharmacological properties of CoS. Specially, we attempt to reveal the antitumor structure-activity relationship (SAR) of CoS-derived triterpenoids. The active substitution sites of CoS, namely, C-3, C-15, C-16, C-21, C-22, C-23, and C-28 pentacyclic triterpenoids, make it a unique and highly valuable substance with significant medicinal and culinary applications. As such, CoS can play a critical role in transforming people's lives, providing unique medicinal benefits, and contributing to the advancement of both medicine and cuisine.

Osteosarcoma is a malignant primary bone tumor, which often associates with pulmonary metastasis. The radical surgery of osteosarcoma often requires internal orthopedic implants. Therefore, implants with antitumor properties should be developed. Magnesium (Mg) and its alloys possess great potential as orthopedic materials, given their biodegradable properties, superior osteogenesis performance, and antitumor features. However, problems arise with their uncontrolled degradation rates and their unknown antitumor mechanisms. In our study, when compared with pure Mg, the rare element silver alloyed with yttrium (Ag–Y) could extremely enhance the corrosion resistance of these elements, giving the Ex–Mg–1Ag–1Y alloy better anticorrosion rates. Here, we implanted the Ex–Mg–1Ag–1Y alloy and pure Mg and Ti alloy in vivo around tumors in nude mice (BALB/c). Notably, the local tumor weight in Mg alloy and pure Mg groups were much smaller than that in Ti alloy group in 36 days after surgery (6.59 ± 0.70, 6.76 ± 0.62, and 8.54 ± 0.56 g), while the general scores of lung metastasis in Mg alloy and pure Mg groups were also lower than Ti alloy group (64.50 ± 7.64, 62.73 ± 7.84, and 87.60 ± 9.43). Therefore, the Mg and Ex–Mg–1Ag–1Y alloy, both demonstrated resisting effects against local tumor growth and pulmonary metastasis, which could be performed by changing the extracellular acidosis microenvironment, elevating the Mg concentration, suppressing C–X–C chemokine receptor type 4 (CXCR4) levels, and increasing prostacyclin (PGI2) synthesis. Our work revealed that the Ex–Mg–1Ag–1Y alloy may be a promising orthopedic implant for treating osteosarcoma due to its better corrosion resistance and antitumor attributes. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2537–2548, 2019. [ABSTRACT FROM AUTHOR]

Copper(II) and zinc(II) complexes with oxindolimine ligands, obtained by a condensation reaction between isatin (1H-indole-2,3-dione) and 2-(2-aminoethyl)pyridine, have been previously shown to activate apoptosis very efficiently in different cancer cell lines. Here, we show that these compounds inhibit human DNA topoisomerase IB (Topo I) activity, and this characteristic may be implicated in its pro-apoptotic and potential antitumor properties. The studied metal complexes prevent DNA relaxation and cleavage reaction, whilst they do not have any effect on the religation process. The protein inhibition occurs in two different ways since the copper compound does not permit the enzyme-DNA complex formation, while the zinc analogue permits this complex formation but inhibits the catalytic cleavage reaction. Other related copper and zinc complexes, one with an asymmetric imine ligand derived from isatin, 1,3-diaminopropane, and salicyladehyde, and another one previously reported, derived from isatin and 1,3-diaminopropane, had their corresponding inhibition results towards Topo I compared. These data demonstrated that such complexes can act as good catalytic inhibitors of Topo I, in a process modulated by the ligand features and the nature of the metal ion. Computational studies complemented and supported experimental data, showing three different characteristics of the metal complexes that influence its interaction and consequent inhibition of Topo I. The ligand planarity when bound to the protein increases the occurring interactions in different binding sites, the total charge of the complex modulates the preferential region of interaction, and the copper(II) complexes are expected to be more efficient inhibitors compared to analogous zinc(II), as verified experimentally. [ABSTRACT FROM AUTHOR]

Phosphoethanolamine (PEA) is a fundamental precursor during the biosynthesis of cell membranes phospholipids. In the past few years, it has been described as a potential antitumor agent. In previous studies, we demonstrated that PEA showed antitumor properties in vitro and in vivo in a wide range of tumor cell lines. Herein, we showed that PEA possesses cytotoxic properties and notably revealed to induce caspase-independent cell death. Of interest, we provided evidence that PEA inhibits melanoma cells proliferation through the reduction of C-RAF. Molecular docking of PEA evidenced that this compound indeed fits satisfactory in the binding site located between the dimers of C-RAF protein with 107,01 Å and score of −29,62. Also, PEA arrested A2058 cells at G2/M phase in the cell cycle. Moreover, cell proliferation, migration and adhesion capacities of A2058 cells were also inhibited by PEA. Most importantly, PEA inhibited tumor growth of melanoma tumors and prolonged survival rate of mice. Also, PEA induced a significant immune response in a syngeneic metastatic melanoma model. Taken together, these data indicate that PEA is a promising candidate for future developments in cancer field. [ABSTRACT FROM AUTHOR]

Self-assembled bovine serum albumin nanoparticles loaded with the isoflavone genistein have shown apoptosis-mediated cytotoxicity against murine mammary adenocarcinoma F3II cells. Due to their protein nature and small particle size (13–15 nm), their parenteral administration could be affected by possible immunogenic reactions and rapid clearance from the bloodstream. To avoid these problems, PEGylation of the systems was achieved in this work by using a 30 kDa methoxy-polyethylene glycol carbonyl imidazole derivative through the reaction between the carbonyl imidazole group and the amino groups of Lys residues on the protein surface, which was confirmed by a 17% reduction in the available amino groups content measured by the o-phthaldialdehyde method. PEGylated isoforms were obtained, showing an increase of particle size from 13 to 15 nm to around 260 nm, and were purified by SEC-FPLC and characterized by SDS-PAGE, DLS and AFM techniques. The effect of PEGylation on BSAnp-Gen cytotoxicity and genotoxicity against F3II cells was evaluated in vitro by MTT assay, flow cytometry analysis and micronucleus assay. From the results, PEGylation produced an improvement of the biological properties of genistein-loaded nanoparticles in terms of cytotoxicity (lower IC 50), not affecting the induction of apoptosis, decreasing the genotoxicity of the systems (less induction of micronucleus formation). [Display omitted] • Bovine serum albumin nanoparticles loaded with genistein (BSAnp-Gen) were PEGylated. • 30 kDa methoxy-polyethylene glycol carbonyl imidazole (mPEG-Im) reacted with Lys amino groups. • Available amino groups in BSAnp-Gen showed a 17% reduction and particle size increased. • BSAnp-Gen cytotoxicity against F3II cells was conserved after PEGylation with lower IC 50. • Genotoxicity (micronucleus formation) on F3II cells was not affected by PEGylation. [ABSTRACT FROM AUTHOR]

L-asparaginase (EC 3.5.1.1), which catalyzes the deamidation of L-asparagine to L-aspartic acid and ammonia, has been widely used as a key therapeutic tool in the treatment of tumors. The current commercially available L-asparaginases, produced from bacteria, have signs of toxicity and hypersensitivity reactions during the course of tumor therapy. Therefore, searching for L-asparaginases with unique biochemical properties and fewer adverse effects was the objective of this work. In this study, cyanobacterial strain Synechococcus elongatus PCC6803 was found as a novel source of L-asparaginase. The L-asparaginase gene coding sequence (gi:939195038) was cloned and expressed in E. coli BL21(DE3), and the recombinant protein ( Se.ASPII) was purified by affinity chromatography. The enzyme has high affinity towards Lasparagine and shows very weak affinity towards L-glutamine. The enzymatic properties of the recombinant enzyme were investigated, and the kinetic parameters ( K , V ) were measured. The pH and temperature dependence profiles of the novel enzyme were analyzed. The work was extended to measure the antitumor properties of the novel enzyme against different human tumor cell lines. [ABSTRACT FROM AUTHOR]

Gold(I), gold(III), silver(I) and copper(I) complexes with modified amino acid esters and phosphine ligands have been prepared in order to test their cytotoxic activity. Two different phosphine fragments, PPh 3 and PPh 2 py (py = pyridine), have been used. The amino acid esters have been modified by introducing an aromatic amine as pyridine that coordinates metal fragments through the nitrogen atom, giving complexes of the type [M(L)(PR 3 )] + or [AuCl 3 (L)] (L = l -valine-N-(4-pyridylcarbonyl) methyl ester ( L1 ), l -alanine-N-(4-pyridylcarbonyl) methyl ester ( L2 ), l -phenylalanine-N-(4-pyridylcarbonyl) methyl-ester) ( L3 ); M = Au(I), Ag(I), Cu(I), PR 3 = PPh 3 , PPh 2 py). The in vitro cytotoxic activity of metal complexes was tested against four tumor human cell lines and one tumor mouse cell line. A metabolic activity test (3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide, MTT) was used and IC 50 values were compared with those obtained for cisplatin . Several complexes displayed significant cytotoxic activities. In order to determine whether antiproliferation and cell death are associated with apoptosis, NIH-3T3 cells were exposed to five selected complexes (Annexin V + FITC, PI) and analyzed by flow cytometry. These experiments showed that the mechanism by which the complexes inhibit cell proliferation inducing cell death in NIH-3T3 cells is mainly apoptotic. [ABSTRACT FROM AUTHOR]

The mushroom Agaricus blazei Murrill was discovered in Piedade, state of São Paulo, Brazil, and sent to Japan to be studied for its medicinal properties. Studies in guinea pigs revealed antitumor properties, triggering Japanese importation of A. blazei from Brazil. Because of its high price on the international market, many companies and rural growers produce A. blazei as alternative crop to increase income, but because interest in this mushroom occurred suddenly there has not been enough time for the scientific community to investigate it and, technology used for its cultivation is still based on empirical rules. There are also some contradicting data regarding the classification of this mushroom, and its antitumor properties still need to be confirmed in humans.

Magnesium (Mg)-based alloys have been regarded as promising implants for future clinic orthopedics, however, how to endow them with good anti-corrosion and biofunctions still remains a great challenge, especially for complicated bone diseases. Herein, three transition metals (M = Mn, Fe, and Co)-containing layered double hydroxides (LDH) (LDH-Mn, LDH-Fe, and LDH-Co) with similar M content are prepared on Mg alloy via a novel two-step method, then systematic characterizations and comparisons are conducted in detail. Results showed that LDH-Mn exhibited the best corrosion resistance, LDH-Mn and LDH-Co possessed excellent photothermal and enzymatic activities, LDH-Fe revealed better cytocompatibility and antibacterial properties, while LDH-Co demonstrated high cytotoxicity. Based on these results, an optimized bilayer LDH coating enriched with Fe and Mn (LDH-MnFe) from top to bottom have been designed for further in vitro and in vivo analysis. The top Fe-riched layer provided biocompatibility and antibacterial properties, while the bottom Mn-riced layer provided excellent anti-corrosion, photothermal and enzymatic effects. In addition, the released Mg, Fe, and Mn ions have a positive influence on angiogenesis and osteogenesis. Thus, the LDH-MnFe showed complementary and synergistic effects on anti-corrosion and multibiofunctions (antibacteria, antitumor, and osteogenesis). The present work offers a novel multifunctional Mg-based implant for treating bone diseases., (© 2022 Wiley-VCH GmbH.)

Abstract: The reactions of N-arylalkyl derivatives of iminodiacetic acid (H2Bnida, H2Peida, H2Ppida, o-H2Cbida; Bn = benzyl, Pe = 2-phenylethyl; Pp = 3-phenylprop-1-yl; o-Cb = o-chlorobenzyl) with sodium tetrachloropalladate(II) in aqueous solutions were investigated. Five new palladium(II) complexes [Pd(HBnida)2]·2H2O (1a), [Pd(HBnida)2] (1b), [Pd(HPeida)2] (2), [Pd(HPpida)2] (3) and [Pd(o-HCbida)2] (4) were prepared and characterized by infrared spectroscopy, 1H, 13C and 15N NMR spectroscopy and thermal analysis (TGA/DTA). The crystal structure of 1a was determined by single-crystal X-ray structural analysis. The palladium(II) ion in the molecule of 1a adopts a square planar coordination with two N,O-bidentate N-benzyl-hydrogeniminodiacetate ions. Complex 1a is a trans-isomer. Antitumor properties of the complexes were tested on three human cell lines. The compounds did not significantly inhibit the growth of colon (HCT 116), breast (MCF-7) and lung (H 460) tumor cell lines. All prepared palladium(II) complexes exhibit the acceptable activities towards the methoxycarbonylation of iodobenzene. [Copyright &y& Elsevier]

Abstract: New stable thiolate gold(I) derivatives containing the alkylated phosphanes [PTA–CH2Ph]Br and [PTA–CH2COOMe]Br derived from 1,3,5-triaza-7-phosphaadamantane (PTA) have been prepared by different routes of synthesis. By the use of basic media to deprotonate the corresponding thiol in the former and by transmetallation reactions from tin (IV) complexes, in the later, thus avoiding side reactions on the phosphane. Strong antiproliferative effects are observed for most of the compounds, including the chloro- and bromo precursors with the series of phosphanes derived from PTA, in human colon cancer cell lines (Caco-2, PD7 and TC7 clones). Apoptosis-induced cell death is found for all compounds, being the thiolate derivatives with [PTA–CH2Ph]Br the most effective, as shown by an annexin-V/propidium iodide double-staining assay. [Copyright &y& Elsevier]

Abstract: Biological properties of a series of aminophosphine-thiolate gold(I) complexes [Au(SR)(PPh2NHpy)] [Ph2PNHpy=2-(diphenylphosphinoamino)pyridine; HSR=2-mercaptopyridine (2-HSpy) (3), 2-mercaptonicotinic acid (2-H2-mna) (4), 2-thiouracil (2-HTU) (5) or 2-thiocytosine (2-HTC) (6)] and [Au(SR){PPh2NH(Htrz)}] [Ph2PNH(Htrz)=3-(diphenylphosphinoamino)-1,2,4-triazole]; HSR=2-mercaptopyridine (2-HSpy) (7), 2-thiocytosine (2-HTC) (8) or 6-thioguanine (6-HTG) (9) have been studied. Their antitumor properties have been tested in vitro against two tumor human cell lines, HeLa (derived from cervical cancer) and MCF-7 (derived from breast cancer), using a metabolic activity test (3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide, MTT). Some of them showed excellent cytotoxic activity. With the aim to obtain more information about the mechanisms of action of these derivatives, the interactions of complexes 3, 5, 7 and 9 with thioredoxin reductase in HeLa cells were studied. They showed a potent inhibition of thioredoxin reductase activity. In order to complete this study, interactions of the complexes with calf thymus (CT-) DNA and with different bacterial DNAs, namely the plasmid pEMBL9 and the promoter region of the furA (ferric uptake regulator A) gene from Anabaena sp. PCC 7120 were investigated. Although interactions of complexes with CT-DNA have been verified, none of them cause significant changes in its structure. [Copyright &y& Elsevier]

Abstract: A novel series of aryloxyalkyl derivatives of imidazole and 1,2,4-triazole, 17–31, was designed and synthesized as inhibitors of heme oxygenase-1 (HO-1) and heme oxygenase-2 (HO-2). Some of these compounds were found to be good inhibitors of HO-1, in particular those carrying an imidazole moiety as azolyl group and a 3-bromo or 4-iodophenyl as aryl moiety. The most potent compounds 6 and 30 were selected and studied for their antitumor properties in a model of LAMA-84 R cell line overexpressing HO-1 and resistant to imatinib mesylate (IM), a tyrosine-kinase inhibitor used in the treatment of multiple types of cancer, most notably Philadelphia Chromosome positive (Ph+) Chronic Myelogenous Leukemia (CML). Results show that both 6 and 30 sensitized LAMA-84 R cell line to antitumor properties of IM. [Copyright &y& Elsevier]

Highlights: [•] The present work describes synthesis and characterization of ternary complexes. [•] Complexes adopt distorted pbp geometry. [•] Extensive H-bonding and π–π interactions are present in complexes. [•] The complexes were screened against tumor cell lines. [•] DNA binding and cleavage experiments were also performed. [Copyright &y& Elsevier]

It was shown using gel-permeation chromatography that arabinogalactan in a SPEX 8000 ball mill changed its molecular-weight distribution (MWD) after mechanochemical treatment. The presence of betulin diacetate assisted the reduction of the MWD after dissolution of the mechanically activated mixture in water and evaporation of the solvent. Complexes of betulin diacetate with arabinogalactan were also obtained as thin films that were readily soluble in water. Mechanical composites of arabinogalactan with betulin diacetate were capable of inducing cell elimination processes mediated by disruption of ionic homeostasis in Ehrlich ascites carcinoma cells. [ABSTRACT FROM AUTHOR]

Abstract: This research work reports the in vitro antitumor personality of few novel peptide nanocomplexes synthesized via a phase-assisted, modified Brust–Schiffrin methodology. Here, a series of metallo(copper, cobalt, nickel and zinc) nanocomplexes engineered with a pre-prepared peptide [N,N′-(1,2-ethylene)-bis-hippuricamide] have been synthesized for damaging the Dalton''s lymphoma ascites tumor model. All the peptide nanocomplexes are spectrally, thermally and morphologically examined. The peptide bound zinc and cobalt nanocomplexes deliver excellent antitumor behavior against both the animal and human cancer cell lines, which has been pre-documented by their efficient DNA damaging skills under physiological conditions. Additionally, all the nanocomplexes are evaluated for the inhibition of microbial augmentation against few fungal and bacterial strains. The above results demonstrate that, a consecutive development of these kinds of peptide nanocomplexes may exemplify their uniqueness in biomedical applications as useful molecular-level devices. [Copyright &y& Elsevier]

Abstract: A hot water-extracted polysaccharide fraction (PFCM) of Passiflora edulis was characterized by microanalysis, infrared spectroscopy, NMR and high performance size-exclusion chromatography. The major component in PFCM is (1→4) linked galacturonic acid (esterified and unesterified). Neutral sugars such as arabinose, glucose, rhamnose, mannose, and fucose were also present. Traces of xylose and ribose were detected. The PFCM sample had a similar molar mass to that of pectin extracted from P. edulis under acidic conditions. Sarcoma 180 tumors treated with PFCM showed a growth inhibition ratio ranging from 40.59% to 48.73% depending on the dosage and type of PFCM administration (oral or intraperitoneal). Toxicological analysis shows that PFCM increases the cell types involved in primary defense mechanisms and no significant changes in the biochemical parameters and organs (e.g., kidney and liver) were observed. However, the use of PFCM treatment increased the spleen weight when compared with the use of 5-fluorouracil. [Copyright &y& Elsevier]

Abstract: Several bioconjugates of ferrocene with biological compounds such as aminoacid esters and related species have been prepared by reaction of chlorocarbonyl ferrocene with the corresponding amino acid ester (histidine methyl ester, tryptophan methyl ester, methionine methyl ester and lysine ethyl ester) or histamine or prolinamide in the presence of NEt3. The reaction of the tryptophan or prolinamide ferrocene conjugates with [Au(acac)(PR3)] (acac=acetylacetonate) results in the substitution of the proton of the cyclic NH groups by the fragment AuPR3 + affording the complexes [Au(FcCO-tryptophan-OMe)(PR3)] or [Au(FcCO-prolinamide)(PR3)] (Fc=ferrocenyl group). The reaction of FcCO-Met-OMe with [Au(OTf)(PR3)] (OTF=trifluoromethysulfonate) or [Au(C6F5)3(OEt2)] yields the gold(I) or gold(III) derivatives [Au(FcCO-Met-OMe)(PR3)]OTf or [Au(C6F5)3(FcCO-Met-OMe)], respectively. Cytotoxicity studies towards several cancer lines such as MCF-7, HeLa or NIE-115 have been performed. The ferrocene bioconjugates show no activity whereas the gold complexes exhibit antiproliferative effect. Preliminary studies of interaction of compounds with cells were carried out with the goal of increasing our knowledge on the mechanism of action of these potential drugs. [Copyright &y& Elsevier]

series of substituted 6-alkyl(6 H)-3-phenyl-1,2,4-triazolo[3,4- b]-1,3,4-thiadiazines have been synthesized by reaction of 3-alkyl-4-amino-5-thio-1,2,4-triazoles with substituted phenacylbromides in the presence of an equimolar amount of KOH. Mass spectra for the dissociative ionization by electron impact, antibacterial activity, and antitumor properties of the synthesized compounds have been studied. It was established that some compounds at doses of 50 - 100 mg/kg decrease the growth of sarcomas 45 and 37 by 35 - 47%. [ABSTRACT FROM AUTHOR]

[Display omitted] • Genistein (Gen) was loaded in heat induced bovine serum albumin nanoparticles (BSAnp). • Gen binding to BSAnp involved hydrophobic and hydrogen bonds interactions. • Colloidal properties of Gen-loaded BSAnp were conserved after freeze drying. • Gen-loaded BSAnp induced dose-dependent cytotoxicity against murine F3II cells. • Main mechanism of cell death for Gen-loaded BSAnp was apoptosis. Antitumor activity of plant-derived flavonoids has been researched during recent decades. Among them, genistein (Gen) stands out for showing cytotoxic activity against breast cancer cells. However, its low water solubility, limited bioavailability, and fast metabolism hinder its administration in chemopreventive therapies. To overcome these obstacles, bovine serum albumin nanovehicles (BSAnp) were obtained by a heat-induced self-assembly process at 70 °C and two aqueous medium pH (9.0 and 11.0) and assayed for the Gen loading. Thus, in this work, Gen loading in BSAnp was studied by spectroscopic techniques and compared with the one obtained for its stereoisomer, chrysin (Chrys). Results revealed that Gen binds to BSAnp via fluorescence quenching mechanism forming inclusion complexes. Compared to Chrys, Gen binding to BSAnp involved more molecules, whereas the association constant was similar for both flavonoids. In general, flavonoid loading in protein systems was strongly affected by the combined effects of BSA conformational state (native vs. aggregated), nanovehicle size, and flavonoid chemical structure. To evaluate the antitumor properties freeze-dried powders were obtained, and they were assayed in vitro after reconstitution by XTT technique and Annexin V-FITC flow cytometry against mouse mammary adenocarcinoma F3II cells. Gen-loaded BSAnp produced a significant decrease in cell viability compared with unloaded BSAnp systems, being the highest cytotoxic effects found for the lowest sized Gen-loaded BSAnp. The leading cytotoxicity mechanism for Gen-loaded systems was apoptosis. Summarizing, it can be concluded that BSAnp constitute versatile nanovehicles for potential flavonoid incorporation in pharmaceutical and nutraceutical matrices. [ABSTRACT FROM AUTHOR]

A divergent route for the synthesis of new derivatives of 4,11-diaminoanthra[2,3-b]thiophene-5,10-dione was developed based on the introduction of cyclic amines to the terminal positions of 4,11-aminoalkyl groups. Modification of the side chains of anthra[2,3-b]-thiophene-5,10-dione increases the affinity of ligands to DNA duplex and decreases the affinity to G-quadruplexes. An analysis of the structure–activity relationship showed that 2-(piperidin-1-yl)ethylamine is the most promising side chain fragment for the development of new double-stranded DNA ligands. The ability of new ligands to bind to DNA duplex correlates with inhibition of tumor cell growth, which indicates the prospects for a further search for new antitumor compounds or chemical probes for duplex-forming nucleic acid sequences among 4,11-diaminoanthra[2,3-b]thiophene-5,10-diones.A divergent route for the synthesis of new derivatives of 4,11-diaminoanthra[2,3-b]thiophene-5,10-dione was developed based on the introduction of cyclic amines to the terminal positions of 4,11-aminoalkyl groups. Modification of the side chains of anthra[2,3-b]-thiophene-5,10-dione increases the affinity of ligands to DNA duplex and decreases the affinity to G-quadruplexes. An analysis of the structure–activity relationship showed that 2-(piperidin-1-yl)ethylamine is the most promising side chain fragment for the development of new double-stranded DNA ligands. The ability of new ligands to bind to DNA duplex correlates with inhibition of tumor cell growth, which indicates the prospects for a further search for new antitumor compounds or chemical probes for duplex-forming nucleic acid sequences among 4,11-diaminoanthra[2,3-b]thiophene-5,10-diones.A divergent route for the synthesis of new derivatives of 4,11-diaminoanthra[2,3-b]thiophene-5,10-dione was developed based on the introduction of cyclic amines to the terminal positions of 4,11-aminoalkyl groups. Modification of the side chains of anthra[2,3-b]-thiophene-5,10-dione increases the affinity of ligands to DNA duplex and decreases the affinity to G-quadruplexes. An analysis of the structure–activity relationship showed that 2-(piperidin-1-yl)ethylamine is the most promising side chain fragment for the development of new double-stranded DNA ligands. The ability of new ligands to bind to DNA duplex correlates with inhibition of tumor cell growth, which indicates the prospects for a further search for new antitumor compounds or chemical probes for duplex-forming nucleic acid sequences among 4,11-diaminoanthra[2,3-b]thiophene-5,10-diones.A divergent route for the synthesis of new derivatives of 4,11-diaminoanthra[2,3-b]thiophene-5,10-dione was developed based on the introduction of cyclic amines to the terminal positions of 4,11-aminoalkyl groups. Modification of the side chains of anthra[2,3-b]-thiophene-5,10-dione increases the affinity of ligands to DNA duplex and decreases the affinity to G-quadruplexes. An analysis of the structure–activity relationship showed that 2-(piperidin-1-yl)ethylamine is the most promising side chain fragment for the development of new double-stranded DNA ligands. The ability of new ligands to bind to DNA duplex correlates with inhibition of tumor cell growth, which indicates the prospects for a further search for new antitumor compounds or chemical probes for duplex-forming nucleic acid sequences among 4,11-diaminoanthra[2,3-b]thiophene-5,10-diones.A divergent route for the synthesis of new derivatives of 4,11-diaminoanthra[2,3-b]thiophene-5,10-dione was developed based on the introduction of cyclic amines to the terminal positions of 4,11-aminoalkyl groups. Modification of the side chains of anthra[2,3-b]-thiophene-5,10-dione increases the affinity of ligands to DNA duplex and decreases the affinity to G-quadruplexes. An analysis of the structure–activity relationship showed that 2-(piperidin-1-yl)ethylamine is the most promising side chain fragment for the development of new double-stranded DNA ligands. The ability of new ligands to bind to DNA duplex correlates with inhibition of tumor cell growth, which indicates the prospects for a further search for new antitumor compounds or chemical probes for duplex-forming nucleic acid sequences among 4,11-diaminoanthra[2,3-b]thiophene-5,10-diones.A divergent route for the synthesis of new derivatives of 4,11-diaminoanthra[2,3-b]thiophene-5,10-dione was developed based on the introduction of cyclic amines to the terminal positions of 4,11-aminoalkyl groups. Modification of the side chains of anthra[2,3-b]-thiophene-5,10-dione increases the affinity of ligands to DNA duplex and decreases the affinity to G-quadruplexes. An analysis of the structure–activity relationship showed that 2-(piperidin-1-yl)ethylamine is the most promising side chain fragment for the development of new double-stranded DNA ligands. The ability of new ligands to bind to DNA duplex correlates with inhibition of tumor cell growth, which indicates the prospects for a further search for new antitumor compounds or chemical probes for duplex-forming nucleic acid sequences among 4,11-diaminoanthra[2,3-b]thiophene-5,10-diones.A divergent route for the synthesis of new derivatives of 4,11-diaminoanthra[2,3-b]thiophene-5,10-dione was developed based on the introduction of cyclic amines to the terminal positions of 4,11-aminoalkyl groups. Modification of the side chains of anthra[2,3-b]-thiophene-5,10-dione increases the affinity of ligands to DNA duplex and decreases the affinity to G-quadruplexes. An analysis of the structure–activity relationship showed that 2-(piperidin-1-yl)ethylamine is the most promising side chain fragment for the development of new double-stranded DNA ligands. The ability of new ligands to bind to DNA duplex correlates with inhibition of tumor cell growth, which indicates the prospects for a further search for new antitumor compounds or chemical probes for duplex-forming nucleic acid sequences among 4,11-diaminoanthra[2,3-b]thiophene-5,10-diones. [ABSTRACT FROM AUTHOR]

A series of phosphino-thiosemicarbazone gold(I) dinuclear complexes obtained by two different synthetic procedures have been prepared. All the compounds have been spectroscopically characterized including single crystal X ray diffraction analysis in some of cases. [Au 2 (HL 1 )Cl 2 (1), [Au 2 (HL 2 ) 2 Cl 2 (2) and [Au 2 (HL 3 ) 2 Cl 2 (3) have been prepared by chemical synthesis using a gold(III) salt as precursor; while [Au 2 (L 1 ) 2 (4), [Au 2 (L 2 ) 2 ∙2CH 3 CN (5) and [Au 2 (L 3 ) 2 (6) have been isolated from an electrochemical synthesis (HLn = 2-[2-(diphenylphosphanyl)-benzylidene]- N -R-thiosemicarbazone; HL1: R = methyl, HL2: R = methoxyphenyl, HL3: R = nitrophenyl). The in vitro cytotoxic activity of these gold(I) complexes was tested against some human tumor cell lines: HeLa 229 (cervical epithelial carcinoma), MCF-7 (ovarian adenocarcinoma), NCI-H460 (non-small-cell lung cancer) and MRC5 (normal human lung fibroblast), and the IC 50 values compared with those of cisplatin. The neutral methyl-substituted complexes 1 and 4 and methoxyphenyl 5 displayed significant cytotoxic activities in all investigated cancer cell lines, being 1 and 4 the most effective. The ability of complexes 1 and 4 to induce cell death by apoptosis in Hela 229 was also investigated by fluorescence microscopy using the apoptotic DNA fragmentation as marker. These results indicated that the inhibition of cell proliferation is mainly due to an apoptotic process. In order to obtain more information about the mechanism of action of these metallocompounds, the interactions of complexes 1 and 4 with the thioredoxin reductase (TrxR) enzyme were analyzed. Both complexes exhibited a strong inhibition of the thioredoxin reductase activity. Unlabelled Image • Gold(I) complexes obtained by traditional and a electrochemical procedures were studied. • Electrochemical synthesis makes available a new arsenal of neutral gold(I) compounds. • Complexes containing the methyl group are the most cytotoxic against the investigated cancer cell lines. • These complexes exhibit a strong inhibition of the thioredoxin reductase activity. [ABSTRACT FROM AUTHOR]

The emodin anthraquinone derivatives are generally used in traditional Chinese medicine due to their various pharmacological activities. In the present study, a series of emodin anthraquinone derivatives have been designed and synthesized, among which 1,3-dihydroxy-6,8-dimethoxyanthracene-9,10-dione is a natural compound that has been synthesized for the very first time, and 1,3-dimethoxy-5,8-dimethylanthracene-9,10-dione is a compound that has never been reported earlier. Interestingly, while total seven of these compounds showed neuraminidase inhibitory activity in influenza virus with inhibition rate more than 50 %, specific four compounds exhibited significant inhibition of tumor cell proliferation. The further results demonstrate that 1,3-dimethoxy-5,8-dimethylanthracene-9,10-dione showed the best anticancer activity among all the synthesized compounds by inducing highest apoptosis rate to HCT116 cancer cells and arresting their G0/G1 cell cycle phase, through elevation of intracellular level of reactive oxygen species (ROS). Moreover, the binding of 1,3-dimethoxy-5,8-dimethylanthracene-9,10-dione with BSA protein has thoroughly been investigated. Altogether, this study suggests the neuraminidase inhibitory activity and antitumor potential of the new emodin anthraquinone derivatives., (© 2020 Wiley-VHCA AG, Zurich, Switzerland.)

Aim: This study aimed to evaluate the antitumor effects of cyclolinopeptide (CL), which suppresses receptor activator of nuclear factor-κB ligand (RANKL) signalling on giant-cell tumours of the bone (GCTB) cells., Materials and Methods: GCTB cell lines were established, and the inhibition of cell growth by CL was evaluated using the water-soluble tetrazolium salt-8 cell proliferation assay, cell cycle assay, and 5-ethynyl-2'-deoxyuridine (EdU) cell proliferation assay. RANKL and runt-related transcription factor 2 (RUNX2) expression levels were evaluated using real-time polymerase chain reaction before and after CL administration., Results: The dose-dependent inhibition of GCTB cells was significantly pronounced in the CL-administered group compared to the non-CL-administered group (p<0.05). In the CL-administered group, the ratio of cells in the G 0 /G 1 phase was increased, but the ratio of EdU-positive cells was decreased (p<0.05). RANKL and RUNX2 levels were decreased in the CL-administered group (p<0.05)., Conclusion: CL has antitumor effects on GCTB in vitro., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)