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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]

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]

[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]

Glioblastoma multiforme (GBM) is a notably lethal brain tumor associated with high proliferation rate and therapeutic resistance, while currently effective treatment options are still lacking. Imidazo[1,2- a ]pyridine derivatives and organoselenium compounds are largely used in medicinal chemistry and drug development. This study is aimed at further investigating the antitumor mechanism of IP-Se-06 (3-((2-methoxyphenyl)selanyl)-7-methyl-2-phenylimidazol[1,2- a ]pyridine), a selenylated imidazo[1,2- a ]pyridine derivative in glioblastoma cells. IP-Se-06 exhibited high cytotoxicity against A172 cells (IC 50 = 1.8  μ M) and selectivity for this glioblastoma cell. The IP-Se-06 compound has pharmacological properties verified in its ADMET profile, especially related to blood-brain barrier (BBB) permeability. At low concentration (1  μ M), IP-Se-06 induced intracellular redox state modulation with depletion of TrxR and GSH levels as well as inhibition of NRF2 protein. IP-Se-06 also decreased mitochondrial membrane potential, induced cytochrome c release, and chromatin condensation. Furthermore, IP-Se-06 induced apoptosis by decreasing levels of Bcl-xL while increasing levels of γ -H2AX and p53 proteins. Treatment with IP-Se-06 induced cell cycle arrest and showed antiproliferative effect by inhibition of Akt/mTOR/HIF-1 α and ERK 1/2 signaling pathways. In addition, IP-Se-06 displayed significant inhibition of p38 MAPK and p-p38, leading to inhibition of inflammasome complex proteins (NLRP3 and caspase-1) in glioblastoma cells. These collective findings demonstrated that IP-Se-06 is a bioactive molecule that can be considered a candidate for the development of a novel drug for glioblastoma treatment., Competing Interests: The authors declare that there are no conflicts of interests., (Copyright © 2022 Daniela C. dos Santos et al.)

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 [IC 50 ] = 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., (© 2020 Wiley Periodicals LLC.)