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Imidazo[1,2‐a]pyridines (IP) and organoselenium compounds have been widely exploited in medicinal chemistry due to their pharmacological activities. Hepatocellular carcinoma (HCC) has few treatment options, and unfortunately, the prognosis is poor. Thus, the development of novel therapeutic drugs is urgent. The present study aimed at evaluating the antitumor mechanism of selenylated IP against HepG2 cells and in vivo. The selenylated IP named IP‐Se‐06 (3‐((2‐methoxyphenyl)selanyl)‐7‐methyl‐2‐phenylimidazol[1,2‐a]pyridine) showed high cytotoxicity against HepG2 cells (half‐maximal inhibitory concentration [IC50] = 0.03 µM) and selectivity for this tumor cell line. At nontoxic concentration, IP‐Se‐06 decreased the protein levels of Bcl‐xL and increased the levels of p53, leading to inhibition of cell proliferation and apoptosis. This compound decreased the level of extracellular signal‐regulated kinase 1/2 protein and changed the levels of proteins involved in the drive of the cell cycle, tumor growth, and survival (cyclin B1, cyclin‐dependent kinase 2). In addition, IP‐Se‐06 decreased the number of cells in the S phase. In addition, IP‐Se‐06 led to increased generation of reactive oxygen species, changed antioxidant defenses, and caused DNA fragmentation. Finally, IP‐Se‐06 significantly inhibited the growth of Ehrlich ascites tumors in mice, increased survival time, and inhibited angiogenesis. Therefore, IP‐Se‐06 may be an important compound regarding the development of a therapeutic drug for HCC treatment. [ABSTRACT FROM AUTHOR]

The purpose of the study was to obtain further in vivo data of antitumor effects and mechanisms triggered by juglone and Q7 in combination with ascorbate. The study was done using Ehrlich ascites tumor-bearing mice. Treatments were intraperitoneal every 24 h for 9 days. Control group was treated with excipient. Previous tests selected the doses of juglone and Q7 plus ascorbate (1 and 100 mg/kg, respectively). Samples of ascitic fluid were collected to evaluate carbonyl proteins, GSH and activity of antioxidant enzymes such as catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase. Hypoxia inducible factor HIF-1α, GLUT1, proteins driving cell cycle (p53, p16 and cyclin A) and apoptosis (poly-ADP-polymerase PARP, Bax and Bcl-xL) were assessed by western blot. Tumor cells were categorized by the phase of cell cycle using flow cytometry and type of cell death using acridine orange/ethidium bromide. A glucose uptake assessment was performed by liquid scintillation using Ehrlich tumor cells cultured with 14 C-deoxyglucose. Treatments caused increased protein carbonylation and activity of antioxidant enzymes and decreased levels of GSH, HIF-1α, GLUT1 and glucose uptake in tumor cells. They also caused increased number of tumor cells in G1, p53 and p16 activation and decreased cyclin A, but only when combined with ascorbate. Apoptosis was induced mostly when treatments were done with ascorbate, causing PARP and Bax cleavage, and increased Bax/Bcl-xL ratio. Juglone and Q7 in combination with ascorbate caused inhibition of tumor progress in vivo by triggering apoptosis and cell cycle arrest associated with oxidative stress, suppression of HIF-1 and uncoupling of glycolytic metabolism. [ABSTRACT FROM AUTHOR]

We describe herein a novel type of monodisperse water-soluble magnetite nanoparticle coated with pheomelanin using an environmentally-friendly approach in aqueous medium. The results indicate superparamagnetic behaviour at room temperature and show improved negative contrast in T2-weighted MRI with a transverse relaxivity of 218 mM−1 s−1. [ABSTRACT FROM AUTHOR]

Supercritical carbon dioxide extracts rich in piperine (SFE) (300 bar; 40 °C) solubilize black pepper ( Piper nigrum ) bioactive phytochemicals with antitumor effect. The aim of this study was to evaluate pro-oxidant status induced by SFE and its effect against Ehrlich ascites carcinoma in Balb-c mouse. Balb/c mice bearing-Ehrlich ascites carcinoma cells (EAC) (male; 22±2 g) received intraperitoneally SFE (100 mg/kg/d; 9 days) or saline. EAC inhibition/survival, antioxidant enzymes activity and GSH content were evaluated. USCF Chimera 1.11.2 /Autodock Vina 1.1.2 default parameters prepared/docked Glutathione Peroxidase (PDB 2OBI; 1.55 Å) and piperine (PubChem CID 638024). SFE inhibit EAC (60%), increasing mice survival (46%) and enhancing activity of superoxide dismutase (4 fold), catalase (56 fold) and glutathione reductase (88%) meanwhile decreased glutatione peroxidase/GPx activity (75%) with GSH depletion (84%). Piperine-GPx poses showed H bonds and hydrophobic interactions near catalytic residues (Cys/Gln/Trp). Therefore, antitumor activity of SFE enhanced EAC pro-oxidative status related with antioxidant enzymes response insufficient to overcome induced oxidative stress. And protein docking suggest the GPx-Piperine interactions could contributed to inhibition of GPx. [ABSTRACT FROM AUTHOR]

[Display omitted] • 4NC & DOX were successfully incorporated in sub-micrometric beeswax-based NLCs. • NLCs had narrow polydispersity, colloidal stability, and semi-spherical shape. • 4NC + DOX-NLCs had the highest inhibition in HepG-2 cells, with additive drug effect. • Combined 4-NC & DOX induced higher apoptosis and reduced ROS generation. Cancer is the second most deadly disease worldwide, and the most traditional approaches such as chemotherapy still face limitations associated to drug dosage and off-target side effects. To address these issues, we propose the simultaneous administration of 4-Nitrochalcone (4NC) and Doxorubicin (DOX) using beeswax based nanostructured lipid carriers (NLCs). The co-encapsulation of 4NC and DOX in the beeswax based NLCs was performed using the water/oil/water double emulsion technique in association with the melt dispersion approach. The system composed by semi-spherical NLCs with an average diameter around 200 nm and narrow size distribution, displayed colloidal stability before and after redispersion, keeping the zeta potential below −30 mV. The antitumor activity of the nanoparticles was screened on different tumor cell lines, and the induced cellular death and internal ROS levels were analyzed on hepatocarcinoma cells, which were found to be more affected by the combination of 4NC and DOX. The results indicated that 4NC + DOX-NCLs could promote cytotoxicity and oxidative damage-mediated apoptosis in a HepG-2 cell line. [ABSTRACT FROM AUTHOR]

A novel series of selenylated imidazo[1,2- a ]pyridines were designed and synthesized with a view to a promising activity against breast cancer cell. The compounds, 7-methyl-3-(naphthalene-1-ylselanyl)-2-phenylimidazo[1,2- a ]pyridine, named IP-Se-05, and 3-((2-methoxyphenyl)selanyl)-7-methyl-2-phenylimidazo[1,2- a ]pyridine, named IP-Se-06, showed high cytotoxicity for MCF-7 cells (IC 50  = 26.0 μM and 12.5 μM, respectively). Both the compounds inhibited the cell proliferation and caused decrease in the number of cells in the G2/M phase of cell cycle. IP-Se-05 and IP-Se-06 were also evaluated for effects on CT-DNA and DNA of MCF-7 cells. The compounds intercalated into CT-DNA and both treatments caused cleavage of DNA in cells. In addition, the compounds induced cell death by apoptosis. However, the presence of (2-methoxyphenyl) selenyl moiety at the imidazo[1,2- a ]pyridine (IP-Se-06) appears to have a better antitumor effect with higher cytotoxicity at a lower concentration and caused less necrosis. Overall, the current study established IP-Se-06 more than IP-Se-05 as a potential prototype compound to be employed as an antiproliferative agent for the treatment of breast cancer. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Ayurvedic and Chinese traditional medicine and tribal people use herbal preparations containing Piper nigrum fruits for the treatment of many health disorders like inflammation, fever, asthma and cancer. In Brazil, traditional maroon culture associates the spice Piper nigrum to health recovery and inflammation attenuation. Aims of the study The aim of the current work was to evaluate the relationship between reactive oxygen species (ROS) overproduction, DNA fragmentation, cell cycle arrest and apoptosis induced by Piper nigrum ethanolic extract and its antitumor activity. Methods The plant was macerated in ethanol. Extract constitution was assessed by TLC, UV–vis and ESI-IT-MS/MS spectrometry. The cytotoxicity, proliferation and intracellular ROS generation was evaluated in MCF-7 cells. DNA damage effects were evaluated through intercalation into CT-DNA, plasmid DNA cleavage and oxidative damage in CT-DNA. Tumor growth inhibition, survival time increase, apoptosis, cell cycle arrest and oxidative stress were assessed in Ehrlich ascites carcinoma-bearing mice. Results Extraction yielded 64 mg/g (36% piperine and 4.2% piperyline). Treatments caused DNA damage and reduced cell viability (EC 50 =27.1±2.0 and 80.5±6.6 µg/ml in MCF-7 and HT-29 cells, respectively), inhibiting cell proliferation by 57% and increased ROS generation in MCF-7 cells (65%). Ehrlich carcinoma was inhibited by the extract, which caused reduction of tumor growth (60%), elevated survival time (76%), cell cycle arrest and induced apoptosis. The treatment with extract increased Bax and p53 and inhibited Bcl-x L and cyclin A expression. It also induced an oxidative stress in vivo verified as enhanced lipid peroxidation and carbonyl proteins content and increased activities of glutathione reductase, superoxide dismutase and catalase. GSH concentration was decreased in tumor tissue from mice. Conclusion The ethanolic extract has cytotoxic and antiproliferative effect on MCF-7 cells and antitumor effect in vivo probably due to ROS overproduction that induced oxidative stress affecting key proteins involved in cell cycle arrest at G1/S and triggering apoptosis. Finally , the overall data from this study are well in line with the traditional claims for the antitumor effect of Piper nigrum fruits. [ABSTRACT FROM AUTHOR]