Normal Human Fibroblast Cells Research Articles

The periodic table of urea derivative: small molecules of zinc(II) and nickel(II) of diverse antimicrobial and antiproliferative applications.

Two complexes of Zn(II) and Ni(II) ions with the urea derivative, 2-benzimidazolyl-urea (BZIMU), of formulae [ZnBZIMU)2(H2O)](NO3)2 (1) and [Ni(BZIMU)2(CH3CH2OH)2](NO3)2 (2) were synthesized and characterized by their melting point, elemental analysis, spectroscopic techniques (FTIR, UV-Vis and 1H-NMR), High-resolution mass spectroscopy (HRMS), molar conductivity and thermogravimetric analysis. The crystal structures of 1-2 were determined by X-ray diffraction analysis. The antiproliferative activity of 1-2 was tested in vitro against human adenocarcinoma cell lines: cervix (HeLa) and breast (MCF-7). Their toxicity was surveyed against normal human fetal lung fibroblast cells (MRC-5). The bioactivity mechanism of 1-2 and their related analogues of copper and silver metallodrugs are rationalized by the means of computations. The antimicrobial activity of 1-2 against Escherichia coli (E. coli) is also evaluated. The complexes [ZnBZIMU)2(H2O)](NO3)2 (1) and [Ni(BZIMU)2(CH3CH2OH)2](NO3)2 (2) (BZIMU= 2-Benzimidazolyl-urea), were tested in vitro against HeLa and MCF-7 cells. Their toxicity was surveyed against normal MRC-5 cells. The association of the microbiota with the antiproliferative activity of 1-2 was investigated against Escherichia coli.

Endogenous H2S-Assisted Cancer-Cell-Specific Activation of Theranostics with Emission Readout.

Realizing the importance of activation of the anticancer drug, its distribution, and for cancer management, a new theranostic probe has been developed. Endogenous H2S stimulated the theranostic molecular prodrug (TP-HS) which is activated in cancer cells; it monitors the actual time of formation of therapeutic agent SN-38 in cellular milieu through fluorescence imaging. Upon exposure to H2S in a similar physiological condition, the azide functionality converted to amine (-NH2) in TP-HS which allows self-immolative scission of the labile benzyl-carbonate moiety for release of rhodol and SN-38 in a concerted manner. Thus, an intense emission band centered at 548 nm has appeared for quantifying the active therapeutic component. The fluorescence image revealed that the TP-HS preferentially releases rhodol and SN-38 in colon cancer (HCT116 cells) and lung cancer cells (A549 cells) compared to normal human fibroblast cells (WI-38). Further, the dose-dependent antiproliferative activity of TP-HS against various cells supports that TP-HS releases SN-38 based on endogenous H2S in cancer cells followed by its apoptotic progression monitored by (a) live-dead, i.e., acridine orange-ethidium bromide double staining assay, (b) APOPercentage apoptotic assay, and (c) Annexin V-FITC staining by flow cytometry. The theranostic prodrug TP-HS showed anticancer efficacy via the desirable apoptotic pathway. It is the first demonstration of a strategic theranostic molecular prodrug system that could be delivered chemotherapeutically with validating the real-time activation of chemotherapy in the cancer cells without the support of a cancer-directing ligand.

Time-dependent AI-Modeling of the anticancer efficacy of synthesized gallic acid analogues

Background/AimMain objective of this study is mapping of the anticancer efficacy of synthesized gallic acid analogues using modeling and artificial intelligence (AI) over a large range of concentrations and exposure times to explore the underline mechanisms of drug action and draw careful inferences regarding drug response heterogeneity. MethodsTwo series of gallic acid derivatives i.e. esters and amides have been synthesized and characterized by FTIR, NMR and mass spectrometry. The compounds have been tested in vitro for their anticancer activity against wild type human ovarian cancer cell line A2780, prostate cancer cell line PC3 and normal human fibroblast cells 3T3. To completely characterize optimal anticancer activity, a comprehensive model using piecewise recursive Hill model is used to quantitatively assess the in vitro anticancer effect of the tested compounds as a function of concentration and exposure time for periods ranging from 24 to 72 h. A robust artificial intelligence approach i.e. the “Support Vector Machine (SVM) Learning Algorithm” is adopted to utilize the data obtained at different temporal values, to identify compounds that trail forecasting algorithm. ResultsAll the synthesized analogues were found biocompatible. Significantly low EC50 values indicated that tested compounds have potent anticancer activity against A2780 cell line in comparison to PC3 cells where only few compounds generated same impact at almost 200 times high dose. On the basis of EC50 values, compounds 7 h, 7 m, 9c, 9b, 7c, 7b and 7 g were identified as the most active anticancer agent against A2780. Three major patterns of drug response heterogeneity were observed for different compounds in the form of multiple Hill graphs and shallow slopes. The anticancer efficiency of the compounds was verified using Machine learning SVM regression learner algorithm. For compounds 7a, 7b, 7e, 7 g, 7o, 7 r, 9b, 9e-9 g higher accuracy was found in predicted and experimentally obtained end point potency in terms of % viability. ConclusionsPharmacodynamics modeling of anticancer potential of the synthesized compounds revealed that drug efficacy and response heterogeneity could be modulated by changing the exposure time to optimize therapeutic impact. Combining experimental results with AI based drug action forecasting, compounds 7b, 7 g, and 9b may be tested further as potent anticancer agent for in vivo studies. This approach may serve a useful tool for extrapolation of in vitro results for generating lead compounds in in vivo and preclinical studies.

Fermentation parameters and conditions affecting levan production and its potential applications in cosmetics

Levan is a polysaccharide composed of fructose units with β-2,6-glycoside bonds. Microorganisms synthesize levan by levansucrase as a mixture of low- and high-molecular-weight fractions. Due to its properties, it has a wide range of applications in cosmetics, pharmaceuticals, food and medicine; it appears that the molecular weight of levan might impact its industrial use. To obtain one fraction of levan after biotransformation, ethanol precipitation with an increasing volume of alcohol was conducted. This precipitation process was also optimized. Several types of analyses were used. Low-molecular-weight levan was evaluated for toxicity in a normal human dermal fibroblast cell line and hemolytic potential on human erythrocytes. Levan was found to be non-cytotoxic and non-hemolytic in concentrations ranging from 0.01 to 1.00 mg/ml. Moreover, levan demonstrated antioxidant potential expressed as an ability to inhibit of oil/water emulsion oxidation and DPPH radical scavenging.

Interactions of zinc(II) complexes with 5′-GMP and their cytotoxic activity

The mechanism of substitution from tetrahedral [ZnCl2(en)] and square-pyramidal [ZnCl2(terpy)] complexes (where en = 1,2-diaminoethane or ethylenediamine and terpy = 2,2′:6′,2′′-terpyridine) by guanosine-5′-monophosphate (5′-GMP) have been investigated by 1H NMR spectroscopy. The substitution reaction of [ZnCl2(terpy)] complex is faster than the reaction of [ZnCl2(en)], which was finished after 48 h. Information about the structures of the final products in solution were obtained from the DFT calculations (B3LYP/6-31G(d)) and experimental 1H NMR data acquired during the course of the reaction. The cytotoxic activity of zinc(II) complexes was tested on human breast cancer cell line MDA-MB-231, human colon cancer cell line HCT-116 and normal human lung fibroblast cell line MRC-5. Both complexes reduced cell viabilities, while [ZnCl2(terpy)] was significantly cytotoxic on MDA-MB-231 after 72 h, and HCT-116 after 24 h without dose dependence. The differences in reactivity toward 5′-GMP and cytotoxic activity of Zn(II) complexes may be attributed to the very stable square-pyramidal geometry of [ZnCl2(terpy)] in solution, while weak ligand effect of the en compared to the terpy affected slow interaction of tetrahedral [ZnCl2(en)] complex with the target bio-molecule.

In situsynthesized chitosan–gelatin/ZnO nanocomposite scaffold with drug delivery properties: Higher antibacterial and lower cytotoxicity effects

ABSTRACTIn this work, chitosan–gelatin/zinc oxide nanocomposite hydrogel scaffolds (CS–GEL/nZnO) were prepared viain situsynthesis of ZnO nanoparticles (nZnO) to reach a scaffold with both inherent antibacterial and drug delivery properties. The prepared nanocomposite hydrogel scaffolds were characterized using scanning electron microscopy, transmission electron microscopy, atomic absorption spectrometer, Fourier transform infrared spectroscopy, and X‐ray diffraction. In addition, swelling, biodegradation, antibacterial, cytocompatibility, and cell attachment of the scaffolds were evaluated. The results showed that the prepared scaffolds had high porosity with a pore size of 50–400 μm and nZnO were well distributed without any agglomeration on the CS–GEL matrix. In addition, the nanocomposite scaffolds showed enhanced swelling, biodegradation, and antibacterial properties. Moreover, the drug delivery studies using naproxen showed that nZnO could control naproxen release. Cytocompatibility of the samples was proved using normal human dermal fibroblast cells (HFF2). In comparison to the previous reports which nZnO were simply added to the matrix of the scaffold,in situsynthesis of nZnO was led to higher antibacterial and lower cytotoxicity effects as a result of well distribution of nZnO in this method. According to the findings, thein situsynthesized CS–GEL/nZnO is strongly recommended for biomedical applications especially skin tissue engineering. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2019,136, 47590.

Synthesis and In Vitro Anticancer Activity of 6-Ferrocenylpyrimidin-4(3H)-one Derivatives.

Some ferrocenyl derivatives are active in vitro and in vivo against cancer. Generally, ferrocenyl derivatives for cancer research have three key components: a ferrocene moiety, a conjugated linker that lowers the oxidation potential and some derivative (peptide, nucleobase and others) that can interact with biomolecules. Since the pyrimidine fragment can easily pass through the membrane into the cells and become involved in metabolism; it appears to be promising. Furthermore, this fragment is an electron-acceptor group, so a spacer can be excluded. Therefore, the synthesis of 6-ferrocenylpyrimidin-4(3H)-one derivatives and the study of their anticancer activity have scientific and practical interest. The syntheses of 6-ferrocenylpyrimidin-4(3H)-one derivatives were performed by the condensation of ethyl 3-ferrocenyl-3-oxopropionate with thiourea or acetamidine or guanidine. The cytotoxicity of four 6- ferrocenylpyrimidin-4(3H)-one derivatives was evaluated by using the MTT assay in vitro against Human breast adenocarcinoma MCF-7 and normal human skin fibroblast HSF cells. The tested derivatives induced a concentration-dependent cytotoxic response in cell lines. A study of the cytotoxic activity of 6-ferrocenylpyrimidin-4(3H)-one derivatives by the MTT test has found that all compounds have a dose-dependent toxic effect on the lines of breast cancer cells (MCF-7) and normal human fibroblast cells (HSF). The most pronounced cytotoxic effect is exhibited by 2-methyl-6-ferrocenylpyrimidin- 4(3H)-one (MCF-7, IC50 17 ± 1 µM). The experimental results confirm the importance of investigation and design of ferrocenylpyrimidin- 4(3H)-one derivatives as anticancer agents. Compounds where the pyrimidine derivatives are directly linked to the ferrocene unit rather than via a spacer group also may be of interest for antiproliferative drug design.

Characterization and DNA methylation modulatory activity of gold nanoparticles synthesized by Pseudoalteromonas strain

Marine extremophiles are shown to tolerate extreme environmental conditions and have high metal reducing properties. Here, we report intracellular synthesis of gold nanoparticles (AuNP) by marine extremophilic bacteria Pseudoalteromonas sp. Bac178 which was isolated from the OMZ of Arabian Sea. Preliminary observations suggest that these bacteria use different pathways which may involves the membrane as well as intracellular proteins for the gold salt reduction. Characterization of the biosynthesised nanoparticles by various techniques such as Scanning electron microscopy (SEM), Transmission electron microscopy (TEM), X-ray diffraction (XRD) and Energy-dispersive X-ray spectroscopy (EDS) confirmed the presence of crystalline gold. These biologically synthesized AuNP were investigated for cytotoxicity and oxidative stress generation in human normal fibroblast and melanoma cells (A375). As AuNP are envisaged to find many applications in the medical field, it was of interest to study the effect of AuNP at the epigenetic level. They were found to be non-cytotoxic, non-genotoxic and non-oxidative stress generating over a range of concentrations. Exposure to these AuNP is observed to cause alterations in global DNA methylation as well as in the expression of DNA methyltransferase (DNMT) genes. Since biosynthesized AuNP are being used in various applications and therapies, their epigenetic modulatory activity needs careful consideration.

Synthesis and anticancer activity of chalcone analogues with sulfonyl groups

Three series of sulfonyl esters were synthesized in reactions of sulfonyl chlorides with three different phenolic chalcone analogues (dehydrozingerone (4-(4-hydroxy-3-methoxyphenyl)-3-buten-2-one), (E)-1-(4-hydroxy-3-methoxyphenyl)pent-1-en-3-one, and (E)-1-(4-hydroxy-3-methoxyphenyl)-5-methylhex-1-en-3-one). The structures of the new compounds were determined by IR, MS, and NMR methods. Screening of the new sulfonyl esters’ in vitro cytotoxic activities against human epithelial cervical carcinoma (HeLa) and normal human fibroblast (MRC-5) cell lines by the MTT method was performed. The five most active were selected and further tested on HeLa, MRC-5, and MCF-7 (breast carcinoma) cell lines. The examined compounds exhibit strong in vitro anticancer activities with moderate-to-high selectivity, inducing apoptotic cell death and cell cycle arrest in both HeLa and MCF-7 cell lines, but have little to no effect on the non-cancerous MRC-5 cell line.

Anti-proliferative effect of auriculataoside A on B16 melanoma 4A5 cells by suppression of Cdc42-Rac1-RhoA signaling protein levels.

Auriculataoside A, an anthracenone dimer glycoside isolated from Cassia auriculata seed, shows anti-proliferative effects on cell line B16 melanoma 4A5 cells with an IC50 value of 0.82μM. However, it shows no such effect on normal human dermal fibroblast (HDF) cells. To evaluate the mode of action underlying the anti-proliferative effect of auriculataoside A on cells, we examined changes in whole protein expression after treatment with auriculataoside A and found that the expression Cdc42, RhoA, and Rac1, which are Rho family GTPases, was reduced. Auriculataoside A also arrested the cell cycle at G1 phase. These results suggest that the suppression of the above proteins induced G1 arrest. In addition, auriculataoside A also suppressed the expression of β-catenin and c-Myc proteins. This action of auriculataoside A could be one of the mechanisms underlying its selective anti-proliferative effect on B16 melanoma cells.

Cytotoxic and Anticancer Effects of ICD-85 (Venom Derived Peptides) in Human Breast Adenocarcinoma and Normal Human Dermal Fibroblasts.

ICD-85 (venom derived peptides) has anti-proliferative effect and anti- angiogenesis activity on cancer cells. This study was performed to test the effect of ICD-85, on Human breast adenocarcinoma (MCF-7) and normal Human Dermal Fibroblasts (HDF) cell lines. In this experimental study, Mitochondrial activity, Neutral red uptake, Lactate dehydrogenase (cell necrosis), and cell morphology were assessed under unexposed and ICD-85 exposed conditions. Caspase-9 colorimetric assay kit was used to determine caspase protease activity. Morphological changes in MCF-7 cells on treatment with ICD-85 compared with untreated MCF-7 cells are consistent with characterizing the features of apoptosis such as granulation and cell rounding which finally results in the generation of apoptotic bodies. In contrast, this difference was not observed in normal cells. In MTT assay, ICD-85 induced dose dependent manner cytotoxic effects on MCF-7 cells which were confirmed by neutral red assay. The results showed that inhibitory concentration 50% (IC50) value of ICD-85 for MCF-7 cells at 24 h was 36.45 ± 0.38 μg/mL. However, when HDF cells were exposed to ICD-85, no significant elevation of LDH release were observed at concentrations below 20 μg/mL. The apoptosis-induction of ICD-85 on MCF-7 cell was found to be through activation of caspase-9 which was 13 fold greater than unexposed cell. This study showed that ICD-85 induced apoptosis in MCF-7 cell line through caspase activation and hence it can be considered for further investigation to use ICD-85 as a potential therapy for breast cancer.

Blockage of glutamine-dependent anaplerosis affects mTORC1/2 activity and ultimately leads to cellular senescence-like response.

ABSTRACTThe purpose of study was to explore the role of glutamine-dependent anaplerosis in cell fate determination (proliferation and senescence) and the potential associated mechanism by employing a pharmacological inhibitor of glutamine-dependent anaplerosis, amino-oxyacetate (AOA). Using the WI38 normal human embryonic fibroblast cell line, we found that exposure to AOA induced mTORC1 inactivation−mTORC2 activation (within day 1), cell cycle arrest (day 2–6) and cellular senescence (day 4–6). These AOA effects were blocked by concomitantly providing anaplerotic factors [α-ketoglutarate (αKG), pyruvate or oxaloacetate], and not affected by ROS scavenger N-acetyl-cysteine (NAC). Moreover, AOA-induced cellular senescence in WI38 cells is associated with elevated protein levels of p53, p21CIP1 and p16INK4A and decreased Rb protein level, which was blocked by αKG supplementation. In p16INK4A-deficient U2OS human osteosarcoma cells and p16INK4A-knockdown WI38 cells, AOA exposure also induced similar effects on cell proliferation, and protein level of P-Rb-S807/811 and Rb. Interestingly, no AOA induction of cellular senescence was observed in U2OS cells, yet was still seen in p16INK4A-knockdown WI38 cells accompanied by the presence of p16 antibody-reactive p12. In summary, we disclose that glutamine-dependent anaplerosis is essential to cell growth and closely associated with mTORC1 activation and mTORC2 inactivation, and impedes cellular senescence particularly associated with p16INK4A.

<i>In Vitro</i> Evaluation System of Pharmacokinetics and Irradiation Effect in Boron Neutron Capture Therapy (BNCT) Using Three-Dimensional Artificial Human Tumor Tissue Model

Boron neutron capture therapy (BNCT) is based on the incorporation of boron-containing drugs to cancer cells and the nuclear reaction of 10B atoms by thermal neutron irradiation results in tumor degeneration. For the development of this therapy, currently, long time and high cost consuming experiments using many animals are required. In this study, we constructed a new in vitro evaluation system for BNCT by combination of an artificial tumor tissue model, comprised of normal human dermal-derived fibroblast (NHDF) and human pancreatic cancer cell line BxPC3, and the optical plastic material CR-39 as a solid state nuclear track detector. Administration of boronophenylalanine (10BPA) as a boron-containing drug and neutron irradiation up to 2.52 × 1012 n/cm2 to the control tissue constructed by NHDF (NHDF3D) and BxPC3 cell loaded tissue (NHDF3D/BxPC3) resulted in detection of 1.6 times higher number of α-ray/recoiled Li particle tracks in NHDF3D/BxPC3 in comparison to NHDF3D, demonstrating that putative irradiation damage to cancer cells can be evaluated by this system. On a cellular level, the hit number of α-ray/recoiled Li particle tracks per single BxPC3 cells and NHDF was evaluated as 5.46 and 1.71, respectively. The tumor and normal tissue ratio (T/N ratio) was 3.19, which was corresponded with those of BPA as 2 - 4 that reported in the previous studies. This new in vitro evaluation system may provide a useful tool for a low cost, labor-saving, and non-animal method for the development of new boron-containing drugs or improvement of BNCT conditions.

Naphthol-derived Betti bases as potential SLC6A14 blockers

Betti bases (aminobenzylnaphthols) have not been studied extensively to explore their possible pharmacological applications. Our group prepared a small and focused library of twenty-three Betti bases from the multicomponent reaction of 2-naphthol with primary or secondary cyclic amines and representative aromatic aldehydes. The compounds were prepared in 52-90% yield using environmentally friendly procedures. The E-factor and the atom economy for our process were 3.92 and 94%, respectively. The study of the anti-proliferative activity against human solid tumor cell lines pointed out that these Betti bases represent privileged scaffolds and could be used for the development of pharmacologically-active compounds in cancer therapeutics. The 50% growth inhibitory (GI50) values of the most potent compounds were in the low micromolar range. Fourteen of these Betti bases were less active in HBL-100 breast cancer cells than towards the breast cancer cell line T-47D. A subset of these Betti bases was further tested against the human breast cancer cell lines MCF-7 and MDA-MB-453. The results indicated a correlation in the sensitivity of T-47D cells to Betti bases. We explored computationally the interaction of the Betti bases with SLC6A14, a Na+- and Cl-- dependent influx transporter of both neutral and cationic amino acids that is overexpressed in T-47D cells. SLC6A14 is inhibited by α-methyl-tryptophan, which blocks cell growth via deprivation of amino acid influx. The docking studies indicated that our Betti bases might behave as tryptophan mimetics, blocking this solute carrier transporter and inducing the anti-proliferative effects. Importantly, these Betti bases showed good cytotoxic selectivity towards cancer cells with no activity against normal human fibroblast cells BJ-hTERT.

Synthesis and biological assay of new 2’-deoxyuridine dimers containing a 1,2,3-triazole linker. Part I

We describe a simple method for the synthesis of modified dinucleosides containing pyrimidine nucleoside analogues (2’-deoxyuridine, thymidine and 5-fluoro-2’-deoxyuridine). Six different dimers with a 1,2,3-triazole linkage were obtained by azide–alkyne 1,3-dipolar cycloaddition (click reaction), starting from propargylated 2’-deoxyuridine and 5’-azido-nucleoside derivatives. Their cytotoxic activity was tested in five human cancer cell lines: cervical (HeLa), high grade gliomas (U-118 MG, U-87 MG, T98G), liver (HepG2), and normal human fibroblast cell line (MRC-5) using the sulforhodamine B (SRB) assay. The experiment showed that the obtained dimers with a 1,2,3-triazole moiety were very stable compounds, also in the physiological-like media, and had no anticancer activity.

Composition, antioxidant capacity and cytotoxic activity of Eugenia uniflora L. chemotype-oils from the Amazon

Ethnopharmacological relevanceOils and extracts of Eugenia uniflora have been reported as antimicrobial, antifungal, antinociceptive, antiprotozoal, antioxidant and cytotoxic. Aim of the studyThe oils of five specimens (E1 to E5) that occur in the Brazilian Amazon were extracted, analyzed for their chemical composition, and submitted to antioxidant and cytotoxic assays. Material and methodsOils were hydrodistilled, analyzed by GC and GC-MS, and submitted to PCA and HCA analyses. The antioxidant activity of the oils was evaluated by the DPPH radical scavenging and the β-carotene/linoleic acid assays. Antiproliferative effects of the oils and curzerene were tested against colon (HCT-116), gastric (AGP-01), and melanoma (SKMEL-19) human cancer cell lines and a normal human fibroblast cell line (MRC-5), using MTT assay. ResultsOxygenated sesquiterpenes and sesquiterpene hydrocarbons such as curzerene, selina-1,3,7(11)-trien-2-one, selina-1,3,7(11)-trien-2-one epoxide, germacrene B, caryophyllene oxide, and (E)-caryophyllene were predominant in the oils. PCA and HCA analyses classified the oils samples into four chemotypes. TEAC values of chemotype II (E3 oil, 228.3 ± 19.2 mg TE/mL) and chemotype III (E4 oil, 217.0 ± 23.3 mg TE/mL) displayed significant antioxidant activities. The oils E2 and E4 showed cytotoxic activity against all cell lines tested HCT-116 (IC50 E2:16.26 μg/mL; IC50 E4:9.28 μg/mL), AGP-01, (IC50 E2:12.60 μg/mL; IC50 E4:8.73 μg/mL), SKMEL-19 (IC50 E2:12.20 μg/mL; IC50 E4:15.42 μg/mL), and MRC-5 (IC50 E2:10.27 μg/mL; IC50 E4:14.95 μg/mL). Curzerene showed the more significant activity against melanoma cells (SKMEL-19, IC50:5.17 μM), induced apoptosis at 5.0 μM and 10.0 μM compared to DMSO, exhibiting a decrease in the cell migration at 5.0 μM and 10.0 μM, after 30 h of treatment. ConclusionThe curzerene chemotype oil and E. uniflora oils can be indicated as drug candidates for anticancer activity of the lung, colon, stomach, and melanoma, with a real prospect to their subsequent phytotherapeutic development.

A novel pro-apoptotic role of zinc octacarboxyphthalocyanine in melanoma me45 cancer cell's photodynamic therapy (PDT)

Zn-based phthalocyanine acts as drug or photosensitizer in photodynamic therapy (PDT) for the treatment of cancer cells. The activated zinc octacarboxyphthalocyanine (ZnPcOC) reacts with oxygen, to generate reactive oxygen species for the damage of melanoma cancer cells, Me45. This in vitro study aimed at investigating the cytotoxic effects of different concentrations of ZnPcOC activated with a diode laser (λ = 685 nm) on Me45, and normal human fibroblast cells, NHDF. To perform this study 104 cells/ml were seeded in 96-well plates and allowed to attach overnight, after which cells were treated with different concentrations of ZnPcOC (10, 20 and 30 μM). After 4 h, cells were irradiated with a constant light dose of 2.5; 4.5 and 7.5 J/cm2. Post-irradiated cells were incubated for 24 h before cell viability was measured using the MTT viability assay. Data indicated that high concentrations of ZnPcOC (30 μM) in its inactive state are not cytotoxic to the melanoma cancer cells and normal fibroblasts. Moreover, the results showed that photoactivated ZnPcOC (30 μM) was able to reduce the cell viability of melanoma and fibroblast to about 50%, respectively. At this photosensitizing concentration the efficacy the treatment light dose of 2.5; 4.5 and 7.5 J/cm2 was evaluated against Me45 cells. ZnPcOC at a concentration of 30 μM activated with a light dose of 2.5; 4.5 and 7.5 J/cm2 was the most efficient for the killing of melanoma cancer cells. Melanoma cancer cells after PDT with a photosensitizing concentration of 30 μM ZnPcOC and a treatment light dose of 2.5; 4.5 and 7.5 J/cm2 showed certain pro-apoptotic characteristics, such as direct inducer (early apoptosis) and long-term inducer, also (late apoptosis). This concludes that low concentrations of ZnPcOC, activated with the appropriate light dose, can be used to induce cell death in melanoma cells via ROS-induces apoptosis pathway, what was confirmed with cytometric ROS measurements.Our in vitro study showed that ZnPcOC mediated photodynamic therapy is an effective treatment option for melanoma Me45 cancer cells. 30 μM of ZnPcOC with the treatment light dose of 2.5 J/cm2 from a LED diode laser source, with a wavelength of 685 nm, was adequate to destroy melanoma cancer cells via ROS-induced apoptosis pathway, with low killing effects on healthy NHDF normal fibroblasts.

Organic Fluorophore Coated Polycrystalline Ceramic LSO:Ce Scintillators for X-ray Bioimaging.

The current effort demonstrates that lutetium oxyorthosilicate doped with 1-10% cerium (Lu2SiO5:Ce, LSO:Ce) radioluminescent particles can be coated with a single dye or multiple dyes and generate an effective energy transfer between the core and dye(s) when excited via X-rays. LSO:Ce particles were surface modified with an alkyne modified naphthalimide (6-piperidin-1-yl-2-prop-2-yn-1-yl-1 H-benzo[ de]isoquinoline-1,3-(2 H)-dione, AlNap) and alkyne modified rhodamine B ( N-(6-diethylamino)-9-{2-[(prop-2-yn-1-yloxy)carbonyl]phenyl}-3 H-xanthen-3-ylidene)- N-ethylethanaminium, AlRhod) derivatives to tune the X-ray excited optical luminescence from blue to green to red using Förster Resonance Energy Transfer (FRET). As X-rays penetrate tissue much more effectively than UV/visible light, the fluorophore modified phosphors may have applications as bioimaging agents. To that end, the phosphors were incubated with rat cortical neurons and imaged after 24 h. The LSO:Ce surface modified with AlNap was able to be successfully imaged in vitro with a low-output X-ray tube. To use the LSO:Ce fluorophore modified particles as imaging agents, they must not induce cytotoxicity. Neither LSO:Ce nor LSO:Ce modified with AlNap showed any cytotoxicity toward normal human dermal fibroblast cells or mouse cortical neurons, respectively.

Synthesis and Antiproliferative Activity of Marine Bromotyrosine Purpurealidin I and Its Derivatives.

The first total synthesis of the marine bromotyrosine purpurealidin I (1) using trifluoroacetoxy protection group and its dimethylated analog (29) is reported along with 16 simplified bromotyrosine derivatives lacking the tyramine moiety. Their cytotoxicity was evaluated against the human malignant melanoma cell line (A-375) and normal skin fibroblast cells (Hs27) together with 33 purpurealidin-inspired simplified amides, and the structure–activity relationships were investigated. The synthesized simplified analogs without the tyramine part retained the cytotoxic activity. Purpurealidin I (1) showed no selectivity but its simplified pyridin-2-yl derivative (36) had the best improvement in selectivity (Selectivity index 4.1). This shows that the marine bromotyrosines are promising scaffolds for developing cytotoxic agents and the full understanding of the elements of their SAR and improving the selectivity requires further optimization of simplified bromotyrosine derivatives.

Evaluation the biological activities of chitosan and O-carboxymethyl chitosan extracted from crab shell waste

The main objective of this study is to prepare chitosan and O-carboxymethyl chitosan and evaluate their biological activities in vitro. In this study, twenty crab shells were collected from locally fish restaurant in the city of Tanta, Egypt. Chitosan has been produced from crab waste by chemical method then modified by introducing carboxymethyl group into its back bone. The antibacterial activity of chitosan and O-carboxymethyl chitosan was tested against multidrug-resistant bacteria by cut-plug method. It was found that the antibacterial activity of modified chitosan was better than the native one. On the other hand, the cytotoxicity of chitosan and O-carboxymethyl chitosan was tested on liver carcinoma cell line HEPG-2 and normal human fibroblast cells (WISH 38). They recorded cytotoxic activities on liver carcinoma cell line, while their toxicities on normal human fibroblast cells were negligible. Finally, their antibacterial activity was evaluated in vivo; the results showed that they were highly active and safe in the treatment of wound infection.