Human Liver Carcinoma Cell Research Articles

Daphnane-type diterpenoids from Euphorbia fischeriana Steud and their cytotoxic activities

Two new daphnane-type diterpenoids fischerianin A (1) and fischerianin B (2), as well as two known ones langduin A (3) and langduin A6 (4), were isolated from the extracts of Euphorbia fischeriana Steud dry roots. Their structures including the absolute stereochemistry were determined by various spectroscopic methods and comparing their experimental and calculated CD spectra. 1 and 2 harbor a ketal group and a 9,13-oxide bridge in their C ring which is rare in daphnane-type diterpenoids. In cytotoxic assays, moderately inhibitory activities of 1–4 against human cancer cell lines (human malignant melanoma cell line, A375; human liver carcinoma cell line, HepG2; human promyelocytic leukemia cell line, HL-60; human Caucasian chronic myelogenous leukemia cell line, K562; human cervix epithelioid carcinoma cell line, HeLa) were observed, with IC50 values ranging from 5.31 to 21.46 μM.

Inhibitory Effect of Delphinidin on Oxidative Stress Induced by H2O2 in HepG2 Cells.

Chronic liver diseases (CLDs) are correlated with oxidative stress induced by the accumulation of intracellular reactive oxygen species (ROS). In this study, we employed HepG2, a human liver carcinoma cell line containing many antioxidant enzymes, to explore the function of delphinidin against oxidative stress induced by H2O2 and to provide scientific data of the molecular mechanism. Cells were pretreated with different concentrations of delphinidin (10 μmol/L, 20 μmol/L, and 40 μmol/L) for 2 h before treatment with 750 μM H2O2 for 1 h. The results showed that H2O2 decreased the survival rate of HepG2 cells and increased the level of ROS, but delphinidin pretreatment could possess the opposite result. At the same time, the expression of Nrf2 was enhanced by the delphinidin pretreatment. This was because delphinidin promoted Nrf2 nuclear translocation and inhibited its degradation, which led to the increase expression of antioxidant protein HO-1 (Nrf2-related phase II enzyme heme oxygenase-1). Besides, we found that delphinidin could significantly alleviate the reduction of Nrf2 protein levels and the accumulation of intracellular ROS levels in Nrf2 knockdown HepG2 cells. In conclusion, our study suggested that delphinidin, as an effective antioxidant, protected HepG2 cells from oxidative stress by regulating the expression of Nrf2/HO-1.

Seaweed-associated heterotrophic bacteria: new paradigm of prospective anti-infective and anticancer agents.

Ever since the development of the first antibiotic compound with anticancer potential, researchers focused on isolation and characterization of prospective microbial natural products with potential anti-infective and anticancer activities. The present work describes the production of bioactive metabolites byheterotrophic bacteria associated with intertidal seaweeds with potential anti-infective and anticancer activities. The bacteria were isolated in a culture-dependent method and were identified as Shewanella algae MTCC 12715 (KX272635) and Bacillus amyloliquefaciens MTCC 12716 (KX272634) based on combined phenotypic and genotypic methods. Further, the bacteria were screened for their ability to inhibit drug-resistant infectious pathogens and prevent cell proliferation of human liver carcinoma (HepG2) and breast cancer (MCF7) cell lines, without affecting the normal cells. Significant anti-infective activity was observed with bacterial cells and their organic extracts against broad-spectrum multidrug-resistant pathogens, such as vancomycin-resistant Enterococcus faecalis, methicillin-resistant Staphylococcus aureus, Klebsiella pneumonia and Pseudomonas aeruginosa with minimum inhibitory concentration ≤ 3.0µgmL-1 as compared to the antibiotic agents' chloramphenicol and ampicillin, which were active at ≥ 6.25mgmL-1. The extracts also exhibited anticancer activity in a dose-responsive pattern against HepG2 (with IC50, half maximal inhibitory concentration ~ 78-83µgmL-1) and MCF7 (IC50 ~ 45-48µgmL-1) on tetrazolium bromide screening assay with lesser cytotoxic effects on normal fibroblast (L929) cell lines (IC50 > 100µgmL-1). The results revealed that seaweed-associated heterotrophic bacteria could occupy a predominant role for a paradigm shift towards the development of prospective anti-infective and anticancer agents.

Anthocyanin-loaded polymeric dextran nanoparticle as an anti-proliferative agent on human liver carcinoma cells

In this communication, anthocyanin-loaded dextran nanoparticles from Clitoria ternatea was synthesized and characterized to test its anti-proliferative activity on the human HepG2 liver cancer cell lines. By using dextran as an encapsulant polymer, the nanoparticles appeared to be spherical, with an average size of 45.5 ± 11 nm. The surface charge of the anthocyanin-loaded dextran nanoparticle was -4.39 mV, which slightly relative to free anthocyanin (-4.46 mV), which indicate good dispersion stabilities. The Fourier transform infrared analysis showed that the anthocyanins from C. ternatea was successfully encapsulated in dextran nanoparticles. Overall, the percentage of drug encapsulation efficiency was 3.03%. Based on the stability test, the anthocyanin-loaded dextran nanoparticle showed significantly better color stability index compared to free anthocyanin, particularly at the presence of light and temperature of 37°C and 50°C. In the anti-proliferation assay on HepG2 liver cancer cell lines, the viability of the cancer cells was significantly reduced after treatment with the anthocyanin-loaded dextran nanoparticle. The anti-proliferation activities of the nanoparticles were significantly better than free anthocyanin. Our findings revealed the ability of the anthocyanin-loaded dextran nanoparticle, in particular from C. ternatea, as an effective anti-proliferative agent against cancer cells. Nanoencapsulation with dextran significantly improve the efficacy and stability of the anthocyanins. Further investigations should be done to evaluate the in vivo efficacy.

Swine acute diarrhea syndrome coronavirus replication in primary human cells reveals potential susceptibility to infection

Zoonotic coronaviruses represent an ongoing threat, yet the myriads of circulating animal viruses complicate the identification of higher-risk isolates that threaten human health. Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a newly discovered, highly pathogenic virus that likely evolved from closely related HKU2 bat coronaviruses, circulating in Rhinolophus spp. bats in China and elsewhere. As coronaviruses cause severe economic losses in the pork industry and swine are key intermediate hosts of human disease outbreaks, we synthetically resurrected a recombinant virus (rSADS-CoV) as well as a derivative encoding tomato red fluorescent protein (tRFP) in place of ORF3. rSADS-CoV replicated efficiently in a variety of continuous animal and primate cell lines, including human liver and rectal carcinoma cell lines. Of concern, rSADS-CoV also replicated efficiently in several different primary human lung cell types, as well as primary human intestinal cells. rSADS-CoV did not use human coronavirus ACE-2, DPP4, or CD13 receptors for docking and entry. Contemporary human donor sera neutralized the group I human coronavirus NL63, but not rSADS-CoV, suggesting limited human group I coronavirus cross protective herd immunity. Importantly, remdesivir, a broad-spectrum nucleoside analog that is effective against other group 1 and 2 coronaviruses, efficiently blocked rSADS-CoV replication in vitro. rSADS-CoV demonstrated little, if any, replicative capacity in either immune-competent or immunodeficient mice, indicating a critical need for improved animal models. Efficient growth in primary human lung and intestinal cells implicate SADS-CoV as a potential higher-risk emerging coronavirus pathogen that could negatively impact the global economy and human health.

Metabolite profiling and evaluation of CYP450 interaction potential of ‘Trimada’- an Ayurvedic formulation

Ethnopharmacological relevanceTrimada is well-known polyherbal Ayurvedic formulation used in Indian Traditional medicine since ancient times. It consisted of three inebriant herbs including “Chitraka” (Plumbago zeylanica Linn. Family- Plumabaginaceae), “Musta” (Cyperus rotundus Linn. Family- Cyperaceae) and Vidanga (Embelia ribes Burm. F. Family- Myrsinaceae) in equal ratios as mentioned in Ayurveda. Trimada is traditionally used to increase the functioning of the digestive system and metabolism. Along with these, it also assists in the reduction of cholesterol as well as reduces stomach aches and chest pain. Aim of the studyThis study is aimed to identify the metabolites present in this polyherbal formulation. Further, the cytotoxicity and interaction potential of the formulation and individual herbs with Cytochrome P450 isozymes (CYP3A4, 2D6, 2C9, 1A2) was evaluated by MTT assay and CYP450 enzyme inhibition. The concentration of heavy metals was also determined. Material and methodsUltra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-QTOF-MS) analysis was performed to detect and identify the phytoconstituents in the formulation. Cytotoxicity of the formulation was evaluated by MTT assay. CYP450 enzyme interaction potential of the individual herbs and the Trimada formulation was carried out through CYP-CO assay and fluorometric high throughput screening (HTS) assay for individual isozymes. The content of heavy metal in the formulation was quantified by Atomic Absorption Spectroscopy. ResultsTrimada formulation exhibited lower cytotoxicity to human liver carcinoma cell line (HepG2). CYP-CO assay revealed that the interaction potential of individual herbs and Trimada on the liver microsomes was found to be lesser than the standard inhibitor ketoconazole. Individual herbs and Trimada formulation displayed higher IC50 values than the respective standard inhibitors in the fluorimetric assay. UPLC-QTOF-MS analysis showed the presence of a number of active phytoconstituents including sesquiterpenes, phenolic acids, benzoquinones, triterpenes and flavonoids. The heavy metal concentration in the traditional medicinal herbal formulation was found within the approved limit. ConclusionsThis study suggested that the individual herbs and Trimada formulation exhibited low cytotoxicity and contributes insignificant interaction with CYP450 isozymes. So, the formulation is considered to be safe for its therapeutic management without any potential drug interaction involving CYP 450 isozymes.

Synthesis, characterization, thermal, DFT computational studies and anticancer activity of furfural-type schiff base complexes

Novel Schiff base ligand N1,N2-bis(furan-2-ylmethylene)-4-methylbenzene-1,2-diamine (L) has been synthesized. The metal complexes of L with metal ions of silver (I), chromium (III), iron (III), cobalt (II), copper (II), cadmium (II), mercury (II), and uranium (VI) were investigated using various spectroscopic techniques (FT-IR, 1H NMR, UV, mass), elemental analysis, TGA, conductivity, X-ray diffraction, fluorescence, and magnetic susceptibility measurements. The conductivity measurements showed the electrolytic nature of the complexes except for Co(II), Cu(II), and Hg(II) complexes. Octahedral geometry was proposed for all complexes except Ag(I) complex that was observed as tetrahedral geometry based on the magnetic moment and spectral studies. The values of optical band gap energy (Eg) of the synthesized complexes and CdO (1.83–3.44 eV) suggested that these compounds could be used as semiconductors. The X-ray diffraction patterns of Schiff base and its complexes were investigated and nano-crystalline size was established for Ag(I), Cr(III), Fe(III), Co(II), Cu(II), and Cd(II) complexes. Theoretical calculations were carried out for the determination of the optimization geometry, vibrational frequencies, energy of HOMO and LUMO as well as the quantum chemical parameters for ligand and its Ag(I), Cr(III), Fe(III), Co(II), Cu(II) and Cd(II) complexes. Furthermore, the photocatalytic properties of the synthesized Fe2O3, Co3O4, CuO, and CdO nanoparticles for degradation of the methylene blue (MB) have been examined. The results showed that combined of H2O2 with catalyst increased the percent of degradation of MB to 83.29, 60.71, 73.70, and 77.24% in 90 min for the nanoparticles Fe2O3 (24 nm), Co3O4 (30 nm), CuO (35 nm), and CdO (74 nm), respectively, which is consistent with particle size. Antimicrobial screening confirmed that Cd(II) complex exhibited greater activity than both ligand and Gentamicin, the reference drug against both Gram-positive and E. coli bacterial strains. In addition, the Hg(II) complex displayed higher activity than both ligand and standard Ketoconazole against fungi. The cytotoxicity of the Cd(II) complex on Human liver carcinoma (Hep-G2) cells showed the highest potent cytotoxicity effect against the growth of carcinoma cells compared to the Vinblastine standard and the ligand.

Mitochondrial dynamics and mitophagy involved in MPA-capped CdTe quantum dots-induced toxicity in the human liver carcinoma (HepG2) cell line.

Quantum dots (QDs) are nanoparticles of inorganic semiconductors and have great promise in various applications. Many studies have indicated that mitochondria are the main organelles for the distribution and toxic effects of QDs. However, the underlying mechanism of QDs interacting with mitochondria and affecting their function is unknown. Here, we report the mechanism of toxic effects of 3-mercaptopropionic acid (MPA)-capped CdTe QDs on mitochondria. Human liver carcinoma (HepG2) cells were exposed to 25, 50 and 100μmol/L of MPA-capped CdTe QDs. The results indicated that MPA-capped CdTe QDs inhibited HepG2 cell proliferation and increased the extracellular release of LDH in a concentration-dependent manner. Furthermore, MPA-capped CdTe QDs caused reactive oxygen species (ROS) generation and cell damage through intrinsic apoptotic pathway. MPA-capped CdTe QDs can also lead to the destruction of mitochondrial cristae, elevation of intracellular Ca2+ levels, decreased mitochondrial transmembrane potential and ATP production. Finally, we showed that MPA-capped CdTe QDs inhibited mitochondrial fission, mitochondrial inner membrane fusion and mitophagy. Taken together, MPA-capped CdTe QDs induced significant mitochondrial dysfunction, which may be caused by imbalanced mitochondrial fission/fusion and mitophagy inhibition. These findings provide insights into the regulatory mechanisms involved in MPA-capped CdTe QDs-induced mitochondrial dysfunction.

Copper (II)-based halogen-substituted chromone antitumor drug entities: Studying biomolecular interactions with ct-DNA mediated by sigma hole formation and cytotoxicity activity

Copper-based antitumor drug entities 1–3 derived from substituted (F−, Br−, –CH3) 3-formylchromone pharmacophore were synthesized and thoroughly characterized by spectroscopic and single X-ray crystallographic studies. These complexes show structural novelty due to presence of the X-bonds in chromone scaffold which could facilitate higher propensity for nucleic acids via sigma σ-hole interactions. Therefore, structure-activity relationship of 1–3 was studied by performing ct-DNA binding, pBR322 cleavage and cytotoxicity activity to validate their potential to act as chemotherapeutic drug entities. The binding studies of 1–3 with ct- DNA were carried out employing many biophysical techniques and the corroborative results of these experiments showed intercalation mode of binding and the order of binding was found to be 2 > 1 > 3. The structure of drug entities could facilitated strong halogen bonding interaction (in case of 1 &2) and stability of X bond was rationalized by sigma hole region of positive electrostatic potential on the surface of C-X covalent bond, as determined by gas phase B3LYP computational DFT studies. Interestingly, 2 exhibited most avid binding affinity due to presence of Br− electron withdrawing and polarizable group. Further, cleavage studies of 1–3 with pBR322 plasmid DNA were performed which demonstrated significant cleavage activity, the supercoiled form (Form I) of plasmid DNA was converted to nicked form (Form II) with the appearance of linearized form (Form III) in between two, implicating lethal double strand breaks of DNA. 2 showed predominantly higher cleavage activity following the similar trend as observed for binding studies. The cytotoxicity of the complexes 1–3 was evaluated by MTT assay against the human liver carcinoma (Huh-7) and prostate cancer (DU-145) cell lines; complex 2 exhibited specific and selective cytotoxicity for the DU-145 cancer cell line with LC50 value of 1.6 μM.

DFT, anticancer, antioxidant and molecular docking investigations of some ternary Ni(II) complexes with 2-[(E)-[4-(dimethylamino)phenyl]methyleneamino]phenol

The biological activities of some ternary nickel complexes with a Schiff base obtained from 4-dimethylaminobenzaldehyde and 2-aminophenol have been reported. The Schiff base (HL1) acts as a primary ligand whereas, anthranilic acid (HL2), 2-nitroaniline (HL3), alanine (HL4) and histidine (HL5) act as secondary ligand or co-ligand. The anticancer activity of these compounds was studied against human colon carcinoma (HCT-116), human hepatocellular liver carcinoma (HEPG-2) and human breast carcinoma (MCF-7) cell lines. As per the results, the compounds were active against the cell lines. The antioxidant activity of the same compounds was evaluated using DPPH (1,1-diphenyl-2-picryl-hydrazyl) radical scavenging and compared with ascorbic acid. The DFT computations for these compounds were made to understand the bonding mode by a GAUSSIAN 09 program. Moreover, a docking analysis using Autodock 4.2 software package was carried out against the tyrosine kinase receptor (PDB ID: 1M17). In addition, QSAR investigation was also performed to understand the biological potency of the ligand.

Cytotoxicity and genotoxicity of Hevea brasiliensis latex C-serum DCS sub-fraction as anticancer agents

Dialysed latex C-serum supernatant (DCS) sub-fraction from the rubber tree (Hevea brasiliensis) was reported to exert significant anti-proliferative effect on specific cancer cell lines, especially in human triple negative breast cancer (MDA-MB-231) and human liver carcinoma (HepG2) cells. In the present study, two human non-cancer origin cell lines, MCF-10A (human breast epithelial cells) and HDFa (human adult dermal fibroblast cells), showed least susceptibility when treated with DCS sub-fraction at concentration range 0–100 µg/mL using 2,5-diphenyl tetrazolium bromide (MTT) assay. Genotoxicity of DCS sub-fraction was assessed through Ames test, in vitro mouse lymphoma assay, and in vitro micronucleus assay. All genotoxicity experiments were tested with the presence and absence of S9 mixture as metabolic activation system. Ames test results showed negative result of mutagenicity as no clear dose-dependent relationship was observed despite mutagenic potential was detected in frame shift-based TA98 and TA1535 Salmonella typhimurium strains. Mouse lymphoma assay produced non-linear dose-dependent effect in experiments without the presence of S9. Meanwhile, experiment with the presence of S9 resulted in an inverse effect of the dose-dependent relationship. In micronucleus assay, the dose-dependent cytotoxicity effect of DCS sub-fraction showed no correlation with the increase number of cells containing micronuclei but appeared to be time-dependent. In conclusion, DCS sub-fraction showed no significant positive results in genotoxicity assays. In vivo genotoxicity assays should be conducted to ensure the safe use of DCS sub-fraction in further exploration for biological applications.

Synthesis, characterization and in vitro analysis of superparamagnetic iron oxide nanoparticles for targeted hyperthermia therapy

Superparamagnetic iron oxide nanoparticles (SPIONs) are considered as promising magnetic nanoheating agents for diagnostic as well as therapeutic applications due to their biocompatibility and tunability of magnetic properties. These nanoheating agents are commonly synthesized by coprecipitation of two iron precursors, though applying less amount of these chemicals may minimize the toxicity risks for biomedical purposes. The aim of this study is to address this issue by considering the high oxidation vulnerability of ferrous ions to ferric ions to synthesize SPIONs via a single-iron precursor under four varied oxidative conditions. The obtained results implied that the properties of SPIONs can be modified by the variation in the oxidizing conditions. Thereby, the optimal sample was produced as the oxygen/nitrogen flow ratio adjusted to 50% in the synthesis environment. The induction heating efficiency of this optimal sample was investigated under the exposure of varied alternating magnetic field (AMF), which resulted in a remarkable specific absorption rate (SAR) of 168.96 W g−1 while maintaining the temperature medium within the secure hyperthermia range. The cytotoxic effect of the optimal SPIONs sample against human liver carcinoma (HepG2) cells was determined using MTT assay, leading to a considerable decrement in the cell viability. The incorporation of SPIONs under the AMF exposure is, therefore, considered as an effectual mechanism to the tumor intervention.

Anti-bacterial, anti-scavenging and cytotoxic activity of garden cress polysaccharides.

Plants polysaccharides are an infinite stock of drug composites with varying pharmacological and biological activities. The present investigation aimed to examine the antibacterial, anti-scavenging and cytotoxic potential of garden cress (GC) polysaccharides. The antibacterial effects vs Escherichia coli and as well as Staphylococcus aureus of GC polysaccharides were examined by means of agar diffusion assay, minimum inhibitory concentration (MIC), outer and inner cell membrane permeability. Antioxidant potential of the GC polysaccharides were performed by free radical DPPH scavenging, superoxide anion scavenging, hydroxyl radical scavenging, reducing power potential assay, and hydrogen peroxide method. Cytotoxicity potential of GC polysaccharides were evaluated by MTT assay in human cervical (HeLa) and liver carcinoma (HepG2) cell lines. The findings showed that GC polysaccharides MIC were 1.06 and 0.56 mg mL−1 against E. coli and S. aureus, respectively. Compared to the standard inhibitor, the GC polysaccharides showed essential inhibitor assays in a very dose dependent approach, and notable actions to scavenge reactive oxygen species (ROS) are also due to the large quantities of hydrophilic polyphenols. The IC50 values of all tested parameters were measured against standard ascorbic acid antioxidant agent. The GC polysaccharides diminish the cell viability percentage of HeLa and HepG2 in a concentration dependent manner. GC polysaccharides at a dose of 500 µg ml−1 exhibited higher anti-tumor activity in both HeLa (65.33 ± 3.75%) and HepG2 (60.33 ± 3.48%). The findings obtained in this study indicate that GC polysaccharides has antibacterial and has a possible source of natural antioxidant and also has cytotoxic effect on different carcinoma cell lines.

PH-sensitive deoxycholic acid dimer for improving doxorubicin delivery and antitumor activity in vivso

To develop simple and effective nano-drug delivery systems remains a major challenge in cancer treatment. Herein, we synthesized an ortho ester-linked deoxycholic acid dimer (DCA-OE), which could effectively self-assemble with doxorubicin (DOX) to form stable nanoparticles (DCA-OE/DOX NPs) by a single emulsion method. DCA-based nanoparticles had a desirable size (∼200 nm), morphology (spherical shape), and high drug encapsulation (drug loading content of ∼18.0 %, drug loading efficiency of ∼77.6 %). DCA-OE could improve the stability and solubility of DOX in physiological environment, while pH-sensitive ortho ester linkage endowed the ability to release DOX quickly in cancer cells. In vitro cytotoxicity and apoptosis verified drug-loaded dimer nanoparticles had similar toxicity with free DOX. Besides, these particles could efficiently accumulate and penetrate into human liver carcinoma cell line (HepG2) multicellular spheroids, thus resulting in enhanced antitumor effect. In vivo tests further exhibited that DCA-OE/DOX NPs had lower systemic toxicity and higher tumor inhibition effect, and its tumor inhibition rate was 84.1 %, which was far more than free DOX (49.3 %). Therefore, the strategy to link functional small molecules with ortho ester has great potentials in specific delivery of anticancer drugs.

Ultrasound-, subcritical water- and ultrasound assisted subcritical water-derived Tartary buckwheat polyphenols show superior antioxidant activity and cytotoxicity in human liver carcinoma cells

The effects of ultrasound-assisted (UAE), subcritical water (SWE) and ultrasound assisted-subcritical water (UA-SWE) treatments on tartary buckwheat polyphenol yield, composition, antioxidant activity and cytotoxicity in human liver carcinoma cells were studied. Folin Ciocalteu assay was used to measure total free phenol content (TFPC), and ABTS, DPPH, FRAP and TEAC assays were used to measure antioxidant activity (AA). Polyphenol characterization was done by LC-MS and cell antioxidant activity (CAA) and cytotoxicity were done using the 2,2′-Azobis-(2-amidinopropane) dihydrochloride [ABAP] and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide [MTT] assays respectively. The highest polyphenol yield was obtained by SWE (53.3 mg g−1), followed by UA-SWE (31.8 mg g−1), UAE (19.3 mg g−1) and HWE (4.2 mg g−1). Also, SWE had the highest TFPC (7.9 mgGAE/gdw). UAE and UA-SWE showed no differences with TFPC being 6.6 and 6.8 mgGAE/gdw, respectively. The control method (HWE) had the largest number of phenolic compounds identified (25), followed by UAE, SWE and UA-SWE which had 20, 13 and 11 phenolics respectively. Beside phenolic acids, all treatments extracted a number of flavonoids such as flavan-3-ols (catechin-7-O-glucoside, epigallocatechin-3-gallate, epigallocatechin, epicatechin), flavonols (kaempferol-3-O-glucoside, kaempferol, kaempferol-3-rutinoside, rutin, quercetin, quercetin-3-O-glucuronide hyperin), flavones (vitexin, isovitexin, orientin, isoorientin) and anthocyanins (cyanidin-3-O-rutinoside, Cyanidin 3-O-galactoside, cyanidin-3-O-glucoside). SWE gave the highest AA for all tests. However, the AA of those obtained by UAE and UA-SWE did not vary (P < 0.05), but were higher than HWE. Different extracts had best AA at different concentrations (HWE, 300; UAE, 250; SWE, 150; UA-SWE, 200 μg/mL). The IC50 of AA were 270.8 ± 21.3, 198.1 ± 16.0, 97.9 ± 13.5, and 150.4 ± 12.8 μg/mL, respectively for HWE, UAE, SWE and UA-SWE. Generally, SWE and UA-SWE showed the highest cytotoxic activities, followed by UAE, with HWE being the lowest. IC50 of cytotoxicity were 76.1 ± 3.3, 79.5 ± 7.0 and 92.6 ± 4.9 µg/mL for SWE, UA-SWE and UAE, respectively. SWE is a promising method for polyphenol extraction and its combination with ultrasound should be optimized for high yield and conservation of bioactivity.

π-Donor/π-Acceptor Interactions for the Encapsulation of Neurotransmitters on Functionalized Polysilicon-Based Microparticles.

Bipyridinium salts, commonly known as viologens, are π-acceptor molecules that strongly interact with π-donor compounds, such as porphyrins or amino acids, leading their self-assembling. These properties have promoted us to functionalize polysilicon microparticles with bipyridinium salts for the encapsulation and release of π-donor compounds such as catecholamines and indolamines. In this work, the synthesis and characterization of four gemini-type amphiphilic bipyridinium salts (1·4PF6–4·4PF6), and their immobilization either non-covalently or covalently on polysilicon surfaces and microparticles have been achieved. More importantly, they act as hosts for the subsequent incorporation of π-donor neurotransmitters such as dopamine, serotonin, adrenaline or noradrenaline. Ultraviolet-visible absorption and fluorescence spectroscopies and high-performance liquid chromatography were used to detect the formation of the complex in solution. The immobilization of bipyridinium salts and neurotransmitter incorporation on polysilicon surfaces was corroborated by contact angle measurements. The reduction in the bipyridinium moiety and the subsequent release of the neurotransmitter was achieved using ascorbic acid, or Vitamin C, as a triggering agent. Quantification of neurotransmitter encapsulated and released from the microparticles was performed using high-performance liquid chromatography. The cytotoxicity and genotoxicity studies of the bipyridinium salt 1·4PF6, which was selected for the non-covalent functionalization of the microparticles, demonstrated its low toxicity in the mouse fibroblast cell line (3T3/NIH), the human liver carcinoma cell line (HepG2) and the human epithelial colorectal adenocarcinoma cell line (Caco-2).

Generation of Stilbene Antimicrobials against Multiresistant Strains of Staphylococcus aureus through Biotransformation by the Enzymatic Secretome of Botrytis cinerea.

The biotransformation of a mixture of resveratrol and pterostilbene was performed by the protein secretome of Botrytis cinerea. Several reaction conditions were tested to overcome solubility issues and to improve enzymatic activity. Using MeOH as cosolvent, a series of unusual methoxylated compounds was generated. The reaction was scaled-up, and the resulting mixture purified by semipreparative HPLC-PDA-ELSD-MS. Using this approach, 15 analogues were isolated in one step. Upon full characterization by NMR and HRMS analyses, eight of the compounds were new. The antibacterial activities of the isolated compounds were evaluated in vitro against the opportunistic pathogens Pseudomonas aeruginosa and Staphylococcus aureus. The selectivity index was calculated based on cytotoxic assays performed against human liver carcinoma cells (HepG2) and the human breast epithelial cell line (MCF10A). Some compounds revealed remarkable antibacterial activity against multidrug-resistant strains of S. aureus with moderate human cell line cytotoxicity.

Synthesis, Characterization, Theoretical Studies, and Antimicrobial/Antitumor Potencies of Salen and Salen/Imidazole Complexes of Co (II), Ni (II), Cu (II), Cd (II), Al (III) and La (III)

Although salens and imidazoles are well‐studied motifs among bioactive and therapeutic agents, their properties when combined in transition metal complexes are not well developed. To explore the structure/reactivity of this class of compounds, a salen‐based ligand, namely (2,2′‐{1,2‐ethanediylbis[nitrilo(E)methylylidene]}diphenol, S), and its binary (MS) and ternary (MSI) complexes (I = imidazole; M = Co (II), Ni (II), Cu (II), Cd (II), Al (III), and La (III)) have been synthesized and fully characterized by standard physicochemical and theoretical methods. Evidence from structural analysis tools along with DFT modeling revealed an unusual monobasic tridentate salen binding mode, involving the phenolic oxygen, the nitrogen of the azomethine group, and NH group formed via phenol‐to‐cyclohexadienone tautomerization, giving rise to a general molecular formula of MSI complexes as [M(S)(I)2(Cl)] for M (II) = Co, Ni, Cu and Cd or [M(S)(I)(Cl)2] for M (III) = Al and La, respectively. The antimicrobial activities of S, MS, and MSI were screened against several bacterial and fungal strains. Of all tested complexes, CdS and CuSI were the most effective antimicrobials, giving larger inhibition zones than the reference antibiotics. The antimicrobial efficacy for the MS complexes follows the order: CdS &gt; gentamicin &gt; CuS &gt; NiS &gt; CoS &gt; LaS &gt; AlS &gt; S, whereas MSI complex, potencies are ordered as CuSI &gt; gentamicin &gt; CdSI &gt;NiSI &gt; CoSI &gt; LaSI &gt; AlSI &gt; S. In vitro cytotoxicity screening of MSI complexes disclosed that both CuSI and CdSI exhibited higher activity against human liver (Hep‐G2) and breast (MDA‐MB231) carcinoma cell lines than the reference (cisplatin) drug. The satisfactory bioactivities observed for several of these compounds supports the underlying design idea for combining important bioactive motifs for possible therapeutic benefit.

Synthesis and in-vitro characterization of superparamagnetic iron oxide nanoparticles using a sole precursor for hyperthermia therapy

Co-precipitation of ferrous and ferric ions is the most common approach for synthesis of superparamagnetic iron oxide nanoparticles (SPIONs). However, reducing the amount of applied chemicals could lessen toxicity risks for biomedical applications. This study aimed to apply the high oxidation vulnerability of ferrous ions for synthesis of SPIONs via a single-precursor route in varied oxidative conditions. The obtained results indicated that physicochemical and magnetic properties of SPIONs were purposefully tunable through alteration of oxidative conditions and the optimized SPIONs were produced when the O2:N2 flow ratio adjusted to 5:5 in synthesis environment. The induction heating efficiency of the optimal SPIONs with different concentrations was evaluated under exposure of various alternating magnetic field (AMF). The cytotoxic activity of these SPIONs on human liver carcinoma (HepG2) cells under hyperthermia condition indicated a noticeable reduction in cell viability to 49 ± 0.3 %, rendering these magnetic nano-heating agents as promising candidates for cancer therapy purposes.

Improved Method for Obtaining of Arctigenin from Arctium Lappa L. and its Antiproliferative Effect on Human Hepatocarcinoma HepG2 Cells

Background: Arctigenin is a lignan found in Arctium lappa L. (Asteraceae) that displays anti-inflammatory activities. Previous studies showed that the crude extract of A. Lappa has antitumor activity in human liver carcinoma, lung and stomach cancer cells. The aim of this study was to obtain arctigenin from A. lappa L., as well as to evaluate its antiproliferative effects in cells of liver carcinoma (HepG2) and fibroblasts (NIH/3T3). Methods: Arctigenin was obtained from the hydrolysis of arctiin, which was isolated from the crude extract of A. lappa. The effects of arctigenin and arctiin on HepG2 cell viability and cell adhesion were analyzed by MTT method. Adhesion assay was also carried out to evaluate the antitumor activity. Results: Our results showed that the analytical process to obtain arctigenin was fast and easy. In vitro experiments showed that arctigenin (107-269 μM) decreased HepG2 cells viability and did not cause cytotoxicity on NIH/3T3 cells. Arctigenin (27-269 μM) demonstrated anti-adhesion in HepG2 cells in a concentration-dependent manner, when compared with control. Conclusion: These results suggest a promising pharmacological activity for arctigenin as an antiproliferative compound.