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Efficient COVID-19 vaccines are widely acknowledged as the best way to end the global pandemic. SARS-CoV-2 receptor-binding domain (RBD) plays fundamental roles related to cell infection. Antibodies could be developed to target RBD and represent a potential approach for the neutralization of the virus. Epitopes used to produce antibodies are generally linear peptides and thus possess multiple confirmations that do not reflect the actual topology of the targeted part in the native protein. On the other hand, macrocyclic epitopes could constitute closer mimics of the native protein topology and, as such, could generate superior antibodies. In this study, we demonstrated the vital effect of the size and the three-dimensional shape of epitopes on the activity of the developed antibodies against the RBD of SARS-CoV-2. The molecular dynamics studies showed the greater stability of the cyclic epitopes compared with the linear counterparts, which was reflected in the affinity of the produced antibodies. The antibodies developed using macrocyclic epitopes showed superiority with respect to binding to RBD compared to antibodies formed from linear peptides. This study constitutes a roadmap for developing superior antibodies that could be used to inhibit the activity of SARS-CoV-2.

Background: Despite significant advances in therapeutic interventions, liver cancer is the leading cause of cancer mortality in the world. Potential phytochemicals have shown to be promising agents against many life-threatening diseases because of their low toxicity and potential effectiveness. Objective: The current study aims to conduct an in vitro investigation of the anticancer activity of Apricot Extract (AE) and Amygdalin Containing Fraction (ACF), additionally studying their therapeutic effects on DMBAinduced liver carcinogenesis mice model to highlight their related biochemical and molecular mechanisms. Methods and Results: Amygdalin was isolated from the seeds of P. armeniaca L. Male mice received AE or ACF, DMBA, DMBA+AE, DMBA+ACF, and vehicles. The oxidative stress and antioxidant markers, cell proliferation by flow cytometric analysis of Proliferating Cell Nuclear Antigen (PCNA) expression, angiogenesis marker (VEGF), inflammatory marker (TNF-α), apoptotic, anti-apoptotic and autophagy genes expression (caspase-3, Bcl-2, and Beclin-1) were investigated. AE and ACF were found to stimulate the apoptotic process by up-regulating caspase-3 expression and down-regulating Bcl-2 expression. They also reduced VEGF and PCNA levels and increased the antioxidant defense system. Moreover, AE and ACF treatments also inhibited HepG2 and EAC cell proliferation and up-regulated Beclin-1 expression. Conclusion: This study provides evidence that, in DMBA-induced hepatocarcinogenesis, the key proteins involved in the proliferation, angiogenesis, autophagy, and apoptosis are feasible molecular targets for hepatotherapeutic potential using AE and ACF.

A solvothermal technique was used to prepare a Zn–benzenetricarboxylic acid (Zn@BTC) organic framework covered with a carboxymethyl cellulose (CMC/Zn@BTC). Fourier transform infrared spectroscopy (FTIR), field emission scanning electron microscope (FESEM), and Brunauer, Emmett, and Teller (BET) surface area were applied to characterize CMC/Zn@BTC. Moreover, the anticancer, anti-migrative, anti-invasive, and anti-proliferative action of CMC/Zn@BTC nanoparticles were assessed on cancer cell lines. Apoptotic markers and DNA damage were assessed to explore the cellular and biological changes induced by CMC/Zn@BTC nanoparticles. The microscopic observation revealed that CMC controls the surface morphology and surface characteristics of the Zn@BTC. The obtained BET data revealed that the Zn@BTC nanocomposite surface area lowers from 1061 m2/g to 740 m2/g, and the pore volume decreases from 0.50 cm3/g to 0.37 cm3/g when CMC is applied to Zn@BTC nanocomposites. The cellular growth of DLD1 and A549 was suppressed by CMC/Zn@BTC, with IC50 values of 19.1 and 23.1 μg/mL, respectively. P53 expression was upregulated, and Bcl-2 expression was downregulated by CMC/Zn@BTC, which promoted the apoptotic process. Furthermore, CMC/Zn@BTC caused DNA damage in both cancer cell lines with diverse impact, 66 percent (A549) and 20 percent (DLD1) compared to cisplatin’s 52 percent reduction. CMC/Zn@BTC has anti-invasive properties and significantly reduced cellular migration. Moreover, CMC/Zn@BTC aims key proteins associated with metastasis, proliferation and programmed cellular death.

This work aimed to measure serum vascular endothelial growth factor (VEGF) levels before and after Conventional transarterial chemoembolization (cTACE) versus drug-eluting beads (DEB)-TACE and evaluate its efficacy in predicting response to therapy and tumor recurrence.114 patients with unresectable hepatocellular carcinoma complicating hepatitis C virus-related cirrhosis were included. They underwent cTACE (58) or DEB-TACE (56). VEGF serum levels were measured before and on days 1 and 30 after TACE. Patients with complete response (CR) after TACE were followed-up for one year. Statistical analysis was done.VEGF level was higher than baseline after cTACE (VEGF serum levels may predict response to therapy in patients treated by DEB-TACE or cTACE but it has no relation to tumor recurrence.

Two crude heteropolysaccharides were isolated from fruits of Caryota mitis and Chamaerops humilis in percentages of 2.65 and 3.89, respectively. In the case of Caryota mitis (CM) polysaccharide, it...

A biologically active agent based on a Zn-1,3,5-benzen tricarboxylic acid (Zn-BTC) framework incorporated into a chitosan (CS) biopolymer (Zn-BTC@CS) was successfully synthesized using a microwave irradiation technique. The synthesized Zn-BTC@CS was characterized using a scanning electron microscope (SEM) and the obtained data indicated a highly smooth surface morphology of the synthesized Zn-BTC and no morphological changes when the Zn-BTC covered the CS. In addition, the particle size diameter varied from 20 to 40 nm. XRD displayed a well-maintained Zn-BTC structure, and the crystal structure of Zn-BTC was not distorted by the composition of Zn-BTC and chitosan in the nanocomposite. Data from BET analysis revealed that the specific surface area of the Zn-BTC was reduced from 995.15 m2/g to 15.16 m2/g after coating with chitosan. The pore size distribution and pore volume of the Zn-BTC, Zn-BTC@CS were centered at 37.26 nm and at 22.5 nm, respectively. Zn-BTC@CS exhibited anticancer efficacy against lung and colon cancer cell lines. Zn-BTC@CS inhibited the proliferation of A549 and DLD-1 cancer cell lines in a dose-dependent manner with IC50 values of 13.2 and 19.8 µg/mL for the colon and lung cancer cell lines, respectively. Zn-BTC@CS stimulated the apoptotic process through up-regulating P53 expression and down-regulating Bcl-2 expression. Moreover, Zn-BTC@CS induced in vitro DNA fragmentation in both cancer cell lines with significantly different affinity by 66% (A549) and 20% (DLD-1) versus 52% reduction by Cisplatin. Zn-BTC@CS (IC50) exhibited anti-invasive activity and dramatically inhibited the migration of lung and colon cancer cell lines. This study provides evidence that Zn-BTC@CS targets the essential proteins involved in proliferation, metastasis, and apoptosis. Thus, Zn-BTC@CS has chemotherapeutic potential for inhibiting lung and colon cancer viability and growth.

A series of thirteen new aryl/hetarylbichalcophene-5-carboxamidines was prepared and screened for an in vitro anti-proliferative activity against sixty cancer cell lines. The tested monocationic bichalcophenes displayed promising potent anticancer activity against most cancer cell lines with GI50 values of 1.34–3.09 μM. The most potent compound was derivative 8 (median GI50 and TGI values of 1.34 and 3.23 μM, respectively), being also the least cytotoxic in this bichalcophene series with an LC50 of 77.6 μM. The most responsive cancer cell lines were leukemia (SR and K-562) and colon (HCT-15 and HT29) with GI50 in the sub-micromolar range. The effect of the tested bichalcophenes on normal human lung fibroblast (WI-38) cell line showed that they exerted their antiproliferative activity outside the realms of causing any toxicity in normal cells. To study apoptotic profiles of representatives of this class, compounds 4h, 4i, and 8 were found to cause significant reductions in cdk1 expression in HCT-116 colon cells by 46, 79, and 84%, respectively versus 52% reduction by 5- Flourouracil (5-FU). These three compounds were also unique being the only derivatives that significantly elevated the expression of p53 by ∼2, 4, and 5 folds, respectively. The tested bichalcophenes exhibited moderate to potent antioxidant activity in DPPH and ABTS as well as hydroxyl radical scavenging assays. Moreover, compounds IIIb, IIIc, 4c, and 4i, showed the highest pro-oxidant activity. Finally, to aid future endeavors for optimization of this series, a 5 descriptor 2D-QSAR model was derived from the common physicochemical parameters of these bichalcophenes and the external validation proved the model's good predictive efficiency.

A new methodology for the synthesis of a new series of mesotetrakis[aryl]-21H,23H-porphyrin derivatives 5a–5d, 6a–6c, 7 and 8 is presented. Structures of new compounds were established based on both elemental and spectral data. Cytotoxicity activity of the newly synthesized compounds was investigated against two human cell lines MCF-7 and HepG2. Molecular docking was performed to investigate the binding between the most active porphyrin derivatives and Bcl-2 molecular biomarkers in HepG2 cells.

This study evaluated the biochemical, molecular, and histopathological mechanisms involved in the hypoglycaemic effect of zinc oxide nanoparticles (ZnONPs) in experimental diabetic rats. ZnONPs were prepared by the sol-gel method and characterised by scanning and transmission electron microscopy (SEM and TEM). To explore the possible hypoglycaemic and antioxidant effect of ZnONPs, rats were grouped as follows: control group, ZnONPs treated group, diabetic group, and diabetic + ZnONPs group. Upon treatment with ZnONPs, a significant alteration in the activities of superoxide dismutase, glutathione peroxidase, and the levels of insulin, haemoglobin A1c, and the expression of cluster of differentiation 4+ (CD4+), CD8+ T cells, glucose transporter type-4 (GLUT-4), tumour necrosis factor, and interleukin-6 when compared to diabetic and their control rats. ZnONPs administration to the diabetic group showed eminent blood glucose control and restoration of the biochemical profile. This raises their active role in controlling pancreas functions to improve glycaemic status as well as the inflammatory responses. Histopathological investigations showed the non-toxic and therapeutic effect of ZnONPs on the pancreas. TEM of pancreatic tissues displayed restoration of islets of Langerhans and increased insulin-secreting granules. This shows the therapeutic application of ZnONPs as a safe anti-diabetic agent and to have a potential for the control of diabetes.

Phytochemicals appeared as a rich source of efficient and safe agents against many diseases like cancer. Various herbal sources are rich in oleanolic acid (OA). The scope of this study was to assess the biochemical and molecular mechanisms implicated in the ameliorative potency of OA against DMBA-induced liver carcinogenesis. Forty-eight male albino mice were assigned randomly to five groups (eight mice each) as follows: control healthy group, olive oil group, OA group, DMBA group, and DMBA with OA. Apoptosis, autophagy, inflammation, proliferation, and angiogenesis were investigated in the tissue samples. Histopathological examination was carried out as well as liver enzymes activity and other hepatic antioxidant and inflammatory biomarkers. The treatment with OA effectively suppressed the DMBA-initiated liver carcinogenesis via modulation of antioxidant status, induction of apoptosis and autophagy through modulating the expression of Caspase-3, Bcl-2 and Beclin-1, inhibiting angiogenesis (VEGF), proliferation (PCNA), and improved liver function and histological picture with a reduction in AFP level. Additionally, OA applies its antitumor effects by inhibition of proinflammatory transcription factor NF-κB and inflammatory markers (TNF-α and Cox-2) associated with DMBA administration. The present study shows that OA treatment efficiently suppressed the DMBA-initiated liver carcinogenesis through induction of mitochondrial-mediated apoptosis and autophagy and modulating inflammation.

The cyclic voltammetry technique was used to study the electrochemical behavior of vanadyl sulfate in absence and presence of antibiotic (cefazolin) in 0.1 M KCl under different pH values at 300.15 K. The redox behavior of vanadyl sulfate has been studied by using glassy carbon electrode, Ag/AgCl as a reference electrode and Pt wire as a counter electrode under potential from +1500 mV to −1000 mV. One anodic peak and one cathodic peak are observed in cyclic voltammograms. Peak current ratio and peak potential separation (ΔE) was calculated, the higher values of them gave an indication about systems under study are quasi-reversible. The effect of pH, scan rate and concentration of electroactive species on the interaction between vanadyl sulfate and antibiotic were studied. Charge transfer coefficients (α), the heterogeneous electron transfer rate constants (ks) and the diffusion coefficients (D) involved in the redox reaction were evaluated.

The structures and thermodynamic parameters of hydrated lithium ion clusters incorporating a single lithium ion and up to six water molecules have been determined with density functional (DFT) and Hartree-Fock (HF) at the RB3LYP/631G(d,p) levels of theory. The possible formed structures are found to be 23 Li + (H 2 O) n complex for n = 1–6. The primary solvation shell in the gas phase is confirmed to be tetrahydrated in aqueous environment. Very important role of intermolecular hydrogen bond in determining the stability of solvation process of different ions is confirmed by theoretical studies. The calculated gas phase coordination number in the first solvation sphere of a hydrated lithium metal ion is found to be four and the same is also confirmed by the experimental findings. The equilibrium lithium–oxygen distance of 1.970 A at the present B3LYP level of study is in excellent agreement with the X-ray diffraction result of 1.980 A and neutron scattering study with a result of 1.90 A for a tetrahydrated lithium cluster. NBO was analyzed and discussed.

An Anton Par Model 55 densimeter was used to measure the densities of copper sulphate solutions in H 2 O and EtOH–H 2 O at 298.15 K, 303.15 K, 308.15 K, and 313.15 K. The acquired information was used to ascertain the apparent molar volumes, limiting partial molar volumes, and transfer partial molar volumes of copper sulphate. These computed parameters were utilized to decipher the solute–solute and solute–solvent interactions of copper sulphate in an aqueous ethanol solution. The ion solvation behavior of copper sulphate in water and aqueous ethanol over the range of 298.15–313.15 K was studied using the electrical conductivity principle. The Kraus–Bray and Shedlovsky models of conductivity were used to analyze the obtained conductance data. From the obtained data, the limiting molar conductance λ ° m , association constant K A , energy of activation of the rating process ( E a ), and related thermodynamic parameters were determined. The Walden product ( λ ° m η 0 ) was determined. The standard thermodynamic parameters of association (Δ G ° A , Δ H ° A ) were calculated and discussed. Increased ion–solvent and solvent–solvent interactions are indicated by limiting molar conductance values with an increasing amount of ethanol. The negative Δ G ° A values indicate that the association processes in all of the studied systems are spontaneous processes. The negative estimation of (Δ H ° A ) demonstrates that the association processes is exothermic in nature.

Silver nanoparticles (AgNPs) were synthesised with hydrothermal autoclaving technique by using AgNO 3 salt (silver precursor) at different concentrations (0.01, 0.1, 0.55, 1.1, 5.5, and 11 mM) and porcine skin (1% (w/v) ) gelatin polymeric matrix (reducing and stabiliser agent). The reaction was performed in an autoclave at 103 kPa and 121°C and the hydrothermal autoclaving exposure time and AgNO 3 molar concentration were varied at a constant porcine skin gelatin concentration. The as-prepared AgNPs were characterised by UV-visible spectroscopy, transmission electron microscopy, and Fourier transform infrared spectroscopy. The antibacterial properties of AgNPs were tested against gram-positive and gram-negative bacteria. Furthermore, 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide and 2,2-diphenyl-1-picrylhydrazyl assays were used to test whether the synthesised AgNPs can be potentially applied in cancer therapy or used as an antioxidant. This approach is a promising simple route for synthesising AgNPs with a smaller average particle 10 nm diameter. Furthermore, AgNPs exhibited a good cytotoxicity activity, reducing the viability of the liver cancer cell line HepG2 with a moderate IC 50 ; they also showed a low-to-fair antioxidant activity. In addition, AgNPs had a remarkable preferential antibacterial activity against gram-positive bacteria than gram-negative bacteria. Therefore, these fabricated AgNPs can be used as an antibacterial agent in curative and preventive health care.

Oilseeds of the plant family Brassicaceae are important for providing both lipid and protein contents to human nutrition. Cruciferins (12S globulins) are seed storage proteins, which are getting attention due to their allergenic and pathogenicity related nature. This study describes the purification and characterization of a trimeric (∼190 kDa) cruciferin protein from the seeds of Brassica nigra (L.). Cruciferin was first partially purified by ammonium sulfate precipitation (30% saturation constant) and further purified by size exclusion chromatography. The N-terminal amino-acid sequence analysis showed 82% sequence homology with cruciferin from Arabidopsis thaliana. The 50–55 kDa monomeric cruciferin produced multiple bands of two major molecular weight ranges (α-polypeptides of 28–32 kDa and β-polypeptides of 17–20 kDa) under reduced conditions of SDS-PAGE. The 2D gel electrophoretic analysis showed the further separation of the bands into their isoforms with major pI ranges between 5.7 and 8.0 (α-polypeptides) and 5.5–8.5 (β-polypeptides). The Dynamic Light Scattering (DLS) showed the monodisperse nature of the cruciferin with hydrodynamic radius of 5.8 ± 0.1 nm confirming the trimeric nature of the protein. The Circular Dichroism (CD) spectra showed both α-helices and β-sheets in the native conformation of the trimeric protein. The pure cruciferin protein (40 mg/ml) was successfully crystallized; however, the crystals diffracted only to low resolution data (8 A). Small-angle x-ray scattering (SAXS) was applied to gain insights into the three-dimensional structure in solution. SAXS showed that the radius of gyration is 4.24 ± 0.25 nm and confirmed the nearly globular shape. The SAXS based ab initio dummy model of B. nigra cruciferin was compared with 11S globulins (PDB ID: 3KGL ) of B. napus which further confirmed a highly similar molecular weight and globular shape indicating a conserved trimerization of B. nigra cruciferin. The comparison of the scattering patterns of both proteins showed a minimized χ2-value of 1.337 confirming a similar molecular structure. This is the first report describing the purification and characterization of a cruciferin protein from seeds of B. nigra.

Nineteen organoselenides were synthesized and tested for their intrinsic cytotoxicity in hepatocellular carcinoma (HepG2) and breast adenocarcinoma (MCF-7) cell lines and their corresponding selective cytotoxicity (SI) was estimated using normal lung fibroblast (WI-38) cells. Most of the organic selenides exhibited good anticancer activity, and this was more pronounced in HepG2 cells. Interestingly, the naphthoquinone- (5), thiazol- (12), and the azo-based (13) organic selenides demonstrated promising SI (up to 76). Furthermore, the amine 4c, naphthoquinone 5, and azo-based 13 and 15 organic selenides were able to down-regulate the expression of Bcl-2 and up-regulate the expression levels of IL-2, IL-6 and CD40 in HepG2 cells compared to untreated cells. Moreover, most of the synthesized candidates manifested good free radical-scavenging and GPx-like activities comparable to vitamin C and ebselen. The obtained results suggested that some of the presented organoselenium candidates have promising anti-HepG2 and antioxidant activities.

Potassium chloride (0.1 M) and acetate buffer of different pH are used to study the redox behavior of Cu(II) ions in absence and presence of lysine amino acid. The potential window +1500 mV and -1000 mV was used to study the redox properties at solid glassy carbon electrode. Silver/silver chloride is used as a reference electrode and the counter electrode used is Pt. One pair of cathodic and anodic peaks for the Cu(II)/Cu(0) system is showed in cyclic voltammograms indicating the presence of two-electron transfer. The interaction between metal and ligand is supported by the shift of peak potential and charge transfer rate constant (k s ) values. Concentration effect of Cu(II) ions and solution pH effect on the interaction was also studied. The quasi-reversible process is indicated by a higher value of peak current ratio and peak potential separation (ΔE).

Here a new series of twenty-one organoselenides, of potential protective activity, were synthesized and tested for their intrinsic cytotoxicity, anti-apoptotic and antioxidant capacities in oligodendrocytes. Most of the organoselenides were able to decrease the ROS levels, revealing antioxidant properties. Compounds 5b and 7b showed a high glutathione peroxidase (GPx)-like activities, which were 1.5 folds more active than ebselen. Remarkably, compound 5a diminished the formation of the oligodendrocytes SubG1 peak in a concentration-dependent manner, indicating its anti-apoptotic properties. Furthermore, based on the SwissADME web interface, we performed an in-silico structure-activity relationship to explore the drug-likeness of these organoselenides, predicting the pharmacokinetic parameters for compounds of interest that could cross the blood-brain barrier. Collectively, we present new organoselenide compounds with cytoprotective and antioxidant properties that can be considered as promising drug candidates for myelin diseases.

8-Hydroxyquinolium chloroacetate (L1) was synthesized and characterized. The results suggest that L1 loses ethyl chloroacetate ion on coordination at low pH (2–5) and consequently it behaves as 8-hydoxyquinoline (L2). Cu2+, Co2+, Pt4+, Pd2+, Au3+, Ag+ and Nd3+ complexes derived from L2 have been synthesized and characterized using spectral, magnetic and thermal measurements. L2 acts as a neutral bidentate ligand in the case of Cu2+, Co2+, Pt4+, Pd2+ and Nd3+ complexes and as a mononegative bidentate ligand in the case of Au3+ and Ag+ complexes. Octahedral geometry is proposed for Cu2+, Co2+ (grey) and Pt4+ complexes and square-planar for Co2+ (green), Pd2+ and Au3+ complexes. The bond lengths, bond angles, chemical reactivities, binding energies and dipole moments for all compounds were evaluated using density functional theory and molecular electrostatic potential for L1. Superoxide dismutase radical scavenger-like activity and cytotoxic activity of the complexes towards HepG2 liver cancer cells has been screened. Cytotoxicity measurements show that Ag+ and Pd2+ complexes have the highest cytotoxic activity while L1, Cu2+, Co2+ (grey), Co2+ (green), Pt4+ and Nd3+ complexes have no cytotoxic activity. Copyright © 2015 John Wiley & Sons, Ltd.

Four previously undescribed sucrose diester of aryldihydronaphthalene-type lignans, named echiumins A-D, were isolated from the butanol fraction of Echium angustifolium Mill, in addition to a known compound, trigonotin A, which is reported for the first time from the title plant. The structures of isolated compounds were elucidated using spectroscopic methods such as HRESIMS and 1D and 2D NMR spectroscopy. The isolated compounds displayed strong to weak antitumor activity against HepG2 and MCF7 cancer cell lines, with echiumins A and D showed the most potent activity.

A new series of Cu2+, Pt4+, Pd2+, Au3+ and Nd3+ complexes derived from 2-(pyridin-1-ium-1-yl) acetate have been synthesized and characterized using elemental analyses, spectral (infrared (IR), UV–visible, mass, 13C NMR and 1H NMR), magnetic and thermal measurements. IR results suggest that the ligand acts in a neutral monodentate fashion in all complexes. Octahedral geometry is proposed for Cu2+ and Pt4+ complexes and square-planar for Pd2+ and Au3+ complexes. The bond lengths, bond angles, and HOMO and LUMO were calculated. Superoxide dismutase-like radical scavenger activity and cytotoxic activity of the isolated complexes on HepG2 liver cancer cells have been screened. Ligand and complexes (Pt4+ and Nd3+) exhibit potent antioxidant activity upon coordination while Cu2+ and Au3+ complexes do not show superoxide dismutase-like radical scavenger activity. The cytotoxic activity assay against HepG2 cell line proves that the ligand and its Pt4+ complex have a high cytotoxic activity, while the other complexes showed no cytotoxic activity. Copyright © 2014 John Wiley & Sons, Ltd.

Novel tetrazole-based diselenides and selenoquinones were synthesized via azido-Ugi and sequential nucleophilic substitution (SN) strategy. Molecular docking study into mammalian TrxR1 was used to predict the anticancer potential of the newly synthesized compounds. The cytotoxic activity of the compounds was evaluated using hepatocellular carcinoma (HepG2) and breast adenocarcinoma (MCF-7) cancer cells and compared with their cytotoxicity in normal fibroblast (WI-38) cells. The corresponding redox properties of the synthesized compounds were assessed employing 2,2-diphenyl-1-picrylhydrazyl (DPPH), glutathione peroxidase (GPx)-like activity and bleomycin dependent DNA damage. In general, diselenides showed preferential cytotoxicity to HepG2 compared to MCF-7 cells. These compounds exhibited also good GPx catalytic activity compared to ebselen (up to 5 fold). Selenoquinones 18, 21, 22 and 23 were selected to monitor the expression levels of caspase-8, Bcl-2 and Ki-67 molecular biomarkers. Interestingly, these compounds downregulated the Bcl-2 and Ki-67 expression levels and activated the expression of caspase-8 in HepG2 cells compared to untreated cells. These results indicate that some of the newly synthesized compounds possess anti-HepG2 activity.

Background Snake venom is a source of many pharmacologically important molecules. Agkistrodon bilineatus commonly known as Cantil, is spread over Central America particularly in Mexico and Costa Rica. From the venom of Agkistrodon bilineatus we have isolated and characterised six hypotensive peptides, and two bradykinin inhibitor peptides. The IC-50 value of four synthesized peptides was studied, towards angiotensin converting enzyme, in order to study the structure-function relationship of these peptides. Results The purification of the peptides was carried out by size exclusion chromatography, followed by reverse phase chromatography. Sequences of all peptides were determined applying MALDI-TOF/TOF mass spectrometry. These hypotensive peptides bear homology to bradykinin potentiating peptides and venom vasodilator peptide. The peptide with m/z 1355.53 (M + H)+1, and the corresponding sequence ZQWAQGRAPHPP, we identified for the first time. A precursor protein containing a fragment of this peptide was reported at genome level, (Uniprot ID P68515), in Bothrops insularis venom gland. These proline rich hypotensive peptides or bradykinin potentiating peptides are usually present in the venom of Crotalinae, and exhibit specificity in binding to the C domain of somatic angiotensin converting enzyme. Four of these hypotensive peptides, were selected and synthesized to obtain the required quantity to study their IC50 values in complex with the angiotensin converting enzyme. The peptide with the sequence ZLWPRPQIPP displayed the lowest IC50 value of 0.64 μM. The IC50 value of the peptide ZQWAQGRAPHPP was 3.63 μM. Conclusion The canonical snake venom BPPs classically display the IPP motif at the C-terminus. Our data suggest that the replacement of the highly conserved hydrophobic isoleucine by histidine does not affect the inhibitory activity, indicating that isoleucine is not mandatory to inhibit the angiotensin converting enzyme. The evaluation of IC 50 values show that the peptide with basic pI value exhibits a lower IC 50 value.

An efficient route towards the synthesis of symmetrical diselenide and seleniumcontaining quinone pseudopeptides via one-pot Ugi and sequential nucleophilic substitution (SN) methodology was developed. Compounds were evaluated for their antimicrobial and anticancer activities and their corresponding antioxidant/pro-oxidant profiles were assesed employing 2,2-diphenyl-1-picrylhydrazyl (DPPH), bleomycin dependent DNA damage and glutathione peroxidase (GPx)-like activity assays. Selenium based quinones were among the most potent cytotoxic compounds with a slight preference for MCF-7 compared to HepG2 cells and good free radical scavenging activity. Furthermore, symmetrical diselenides exhibited the most potent GPx-like activity compared to ebselen. Moreover, compounds 7, 8, 9 and 10 exhibited similar antifungal activity to the antifungal drug clotrimazole with modest activity against the Gram-positive bacterium S. aureus. These results indicate that some of the synthesized organoselenides are redox modulating agent with promising anti-cancer and antifungal potentials.

Oxidative stress (OS) and disturbed intracellular redox balance have been predominantly observed in different types of cancer, including hepatocellular carcinoma (HCC). Agents which can stop OS multi-stressor events and modulate the intracellular redox state are becoming a major focus in HCC prevention. Among them, compounds with glutathione peroxidase (GPx)-like activity are of particularly concern. We herein report the synthesis of novel series of organoselenocyanates and symmetrical diselenide antioxidants, inspired by the natural redox enzyme, GPx and the synthetic organoselenium ebselen antioxidants. Their cytotoxic activity was evaluated against Hep G2 cells and their antimicrobial activities were evaluated against Candida albicans ( C. albicans ) fungus as well as against Escherichia coli ( E. coli ) and Staphylococcus aureus ( S. aureus ), gram-negative and gram-positive bacteria, respectively. These compounds were also tested for their antioxidant activities using 2,2-diphenyl-1-picrylhydrazyl (DPPH), GPx-like activity and bleomycin dependent DNA damage assays and a basic structure–activity relationship was subsequently established. The physicochemical parameters and drug-likeness were computed employing the Molinspiration online property calculation toolkit and MolSoft software. Interestingly, some compounds proved to be more cytotoxic than ebselen and the known anticancer drug 5-Fu and in the same time they showed similar, sometime even more, antifungal activity than the reference antifungal drugs. Among these compounds, compound 16 was considered to be the most interesting with free radical-scavenging activity comparable to ascorbic acid and a GPx-like activity similar to ebselen. As most of these compounds comply with Lipinski's Rule of Five, they promise good bioavailability, which needs to be studied as part of future investigations.

Hepatocellular carcinoma (HCC) is a dreaded malignancy that every year causes half a million deaths worldwide. Being an aggressive cancer, its incidence exceeds 700,000 new cases per year worldwide with a median survival of 6-8 months. Despite advances in prognosis and early detection, effective HCC chemoprevention or treatment strategies are still lacking, therefore its dismal survival rate remains largely unchanged. This review will characterize currently available chemotherapeutic drugs used in the treatment of HCC. The respective mode(s) of action, side effects and recommendations will be also described for each drug.

A 55 kDa cruciferin protein has been purified and characterized from seeds of Moringa oleifera plant. Protein blast of N-terminal amino-acid sequence showed 60 % sequence similarity with cruciferin from Brassica napus. The M. oleifera protein has been crystallized applying the sitting drop method using 5 % polyethylene glycol 8,000, 38.5 % 3-methyl-1,5-pentanediol and 0.1 M sodium cacodylate pH 6.5. The crystals belonged to the P6322 hexagonal space group with cell dimensions, a = b = 98.4, c = 274.3 A. Initial diffraction data have been collected to a resolution of 6 A.