Mn(II) Polypyridyl Complexes: Precursors to High Valent Mn(V)=O Species and Inhibitors of Cancer Cell Proliferation.

The reaction of [(L)MnII ]2+ (L = neutral polypyridine ligand framework) in the presence of mCPBA (mCPBA = m-Chloroperoxybenzoic acid) generates a putative MnV =O species at RT. The proposed MnV =O species is capable of performing the aromatic hydroxylation of Cl-benzoic acid derived from mCPBA to give [(L)MnIII (m-Cl-salicylate)]+ , which in the presence of excess mCPBA generates a metastable [(L)MnV (O)(m-Cl-salicylate)]+ , characterized by UV/Vis absorption, EPR, resonance Raman spectroscopy, and ESI-MS studies. The current study highlights the fact that [(L)MnIII (m-Cl-salicylate)]+ formation may not be a dead end for catalysis. Further, a plausible mechanism has been proposed for the formation of [(L)MnV (O)-m-Cl-salicylate)]+ from [(L)MnIII (m-Cl-salicylate)]+ . The characterized transient [(L)MnV (O)-m-Cl-salicylate)]+ reported in the current work exhibits high reactivity for oxygen atom transfer reactions, supported by the electrophilic character depicted from Hammett studies using a series of para-substituted thioanisoles. The unprecedented study starting from a non-heme neutral polypyridine ligand framework paves a path for mimicking the natural active site of photosystem II under ambient conditions. Finally, evaluating the intracellular effect of Mn(II) complexes revealed an enhanced intracellular ROS and mitochondrial dysfunction to prevent the proliferation of hepatocellular carcinoma and breast cancer cells.

Different Ability of Multidrug-Resistant and -Sensitive Counterpart Cells to Release and Capture Extracellular Vesicles.

Cancer multidrug resistance (MDR) is one of the main challenges for cancer treatment efficacy. MDR is a phenomenon by which tumor cells become resistant to several unrelated drugs. Some studies have previously described the important role of extracellular vesicles (EVs) in the dissemination of a MDR phenotype. EVs' cargo may include different players of MDR, such as microRNAS and drug-efflux pumps, which may be transferred from donor MDR cells to recipient drug-sensitive counterparts. The present work aimed to: (i) compare the ability of drug-sensitive and their MDR counterpart cells to release and capture EVs and (ii) study and relate those differences with possible distinct fate of the endocytic pathway in these counterpart cells. Our results showed that MDR cells released more EVs than their drug-sensitive counterparts and also that the drug-sensitive cells captured more EVs than their MDR counterparts. This difference in the release and capture of EVs may be associated with differences in the endocytic pathway between drug-sensitive and MDR cells. Importantly, manipulation of the recycling pathway influenced the response of drug-sensitive cells to doxorubicin treatment.

Rapid Disulfide Mapping in Peptides and Proteins by meta-Chloroperoxybenzoic Acid (mCPBA) Oxidation and Tandem Mass Spectrometry.

Disulfide bonds are a class of important post-translational modifications that play important roles in modulating the structures and functions of proteins. Therefore, the mapping of disulfide linkages in peptides and proteins is indispensable for complete structure characterization and functional studies. As disulfide bonds in protonated ions do not dissociate readily under low-energy collision-induced dissociation (CID), they are usually chemically cleaved or activated prior to mass spectrometry (MS) or tandem MS (MS/MS) analysis. In this study, we report a new method that allows the mapping of disulfide linkages in peptides and proteins through meta-chloroperoxybenzoic acid (mCPBA)-based disulfide oxidation and MS/MS. Upon oxidation, the disulfide bond is converted to a thiosulfinate group, i.e., S(═O)-S, in a rapid (>60% yield in 1 min) and highly specific approach in an aqueous phase. The thiosulfinate group is then preferentially cleaved by MS/MS. For interchain disulfide linkages, this leads to a facile peptide chain separation and the identification of disulfide-linked peptides. For intrachain disulfide linkages, collisional activation of the thiosulfinate leads to disulfide cleavage and fragmentation of the peptide backbone constrained by the disulfide loop, enabling a near-complete peptide sequencing. The mCPBA oxidation-based disulfide mapping strategy can be readily integrated with bottom-up or top-down protein analysis for comprehensive protein structure elucidation, e.g., digested lysozyme and intact human insulin.

Revisiting Alkane Hydroxylation with m-CPBA (m-Chloroperbenzoic Acid) Catalyzed by Nickel(II) Complexes.

Mechanistic studies are performed on the alkane hydroxylation with m-CPBA (m-chloroperbenzoic acid) catalyzed by nickel(II) complexes, NiII (L). In the oxidation of cycloalkanes, NiII (TPA) acts as an efficient catalyst with a high yield and a high alcohol selectivity. In the oxidation of adamantane, the tertiary carbon is predominantly oxidized. The reaction rate shows first-order dependence on [substrate] and [NiII (L)] but is independent on [m-CPBA]; vobs =k2 [substrate][NiII (L)]. The reaction exhibited a relatively large kinetic deuterium isotope effect (KIE) of 6.7, demonstrating that the hydrogen atom abstraction is involved in the rate-limiting step of the catalytic cycle. Furthermore, NiII (L) supported by related tetradentate ligands exhibit apparently different catalytic activity, suggesting contribution of the NiII (L) in the catalytic cycle. Based on the kinetic analysis and the significant effects of O2 and CCl4 on the product distribution pattern, possible contributions of (L)NiII -O. and the aroyloxyl radical as the reactive oxidants are discussed.

Synthesis, Characterization, DNA/HSA Interactions, and Anticancer Activity of Two Novel Copper(II) Complexes with 4-Chloro-3-Nitrobenzoic Acid Ligand.

The purpose of this study was to identify new metal-based anticancer drugs; to this end, we synthesized two new copper(II) complexes, namely [Cu(ncba)4(phen)] (1) and [Cu(ncba)4(bpy)] (2), comprised 4-chloro-3-nitrobenzoic acid as the main ligand. The single-crystal XRD approach was employed to determine the copper(II) complex structures. Binding between these complexes and calf thymus DNA (CT-DNA) and human serum albumin (HSA) was explored by electronic absorption, fluorescence spectroscopy, and viscometry. Both complexes intercalatively bound CT-DNA and statically and spontaneously quenched DNA/HSA fluorescence. A CCK-8 assay revealed that complex 1 and complex 2 had substantial antiproliferative influences against human cancer cell lines. Moreover, complex 1 had greater antitumor efficacy than the positive control cisplatin. Flow cytometry assessment of the cell cycle demonstrated that these complexes arrested the HepG2 cell cycle and caused the accumulation of G0/G1-phase cells. The mechanism of cell death was elucidated by flow cytometry-based apoptosis assays. Western blotting revealed that both copper(II) complexes induced apoptosis by regulating the expression of the Bcl-2(Bcl-2, B cell lymphoma 2) protein family.

Discovery of JMJD7 inhibitors with the aid of virtual screening and bioactivity evaluation.

Jumonji-C (JmjC) domain-containing 7 (JMJD7), which is a 2-oxoglutarate (2OG)-dependent oxygenase, has been demonstrated to play an important role in the occurrence and development of a number of diseases, particularly cancer. Discovery of JMJD7 inhibitors is thus of great importance. Herein consensus docking/scoring strategy and bioactivity evaluation were used to identify JMJD7 inhibitors from various chemical databases. Seven active compounds were retrieved. The most potent compound, Cpd-3, showed an IC50 value of 6.62 µM against JMJD7. Further biophysical assays confirmed that Cpd-3 could efficiently bind to JMJD7 in vitro. Flexible docking was used to predict the binding mode of Cpd-3 with JMJD7. In a cellular assay, Cpd-3 displayed good inhibitory activity against cancer cell lines expressing a high level of JMJD7. As far as we know, Cpd-3 is the first JMJD7 inhibitor reported so far. Overall, this study established a good starting point for drug discovery targeting JMJD7.

New Tetrahydroacridine Hybrids with Dichlorobenzoic Acid Moiety Demonstrating Multifunctional Potential for the Treatment of Alzheimer's Disease.

A series of new tetrahydroacridine and 3,5-dichlorobenzoic acid hybrids with different spacers were designed, synthesized, and evaluated for their ability to inhibit both cholinesterase enzymes. Compounds 3a, 3b, 3f, and 3g exhibited selective butyrylcholinesterase (EqBuChE) inhibition with IC50 values ranging from 24 to 607 nM. Among them, compound 3b was the most active (IC50 = 24 nM). Additionally, 3c (IC50 for EeAChE = 25 nM and IC50 for EqBuChE = 123 nM) displayed dual cholinesterase inhibitory activity and was the most active compound against acetylcholinesterase (AChE). Active compound 3c was also tested for the ability to inhibit Aß aggregation. Theoretical physicochemical properties of the compounds were calculated using ACD Labs Percepta and Chemaxon. A Lineweaver-Burk plot and docking study showed that 3c targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Moreover, 3c appears to possess neuroprotective activity and could be considered a free-radical scavenger. In addition, 3c did not cause DNA damage and was found to be less toxic than tacrine after oral administration; it also demonstrated little inhibitory activity towards hyaluronidase (HYAL), which may indicate that it possesses anti-inflammatory properties. The screening for new in vivo interactions between 3c and known receptors was realized by yeast three-hybrid technology (Y3H).

Iron-Catalyzed C(sp2)-C(sp3) Cross-Coupling of Aryl Chlorobenzoates with Alkyl Grignard Reagents.

Aryl benzoates are compounds of high importance in organic synthesis. Herein, we report the iron-catalyzed C(sp2)-C(sp3) Kumada cross-coupling of aryl chlorobenzoates with alkyl Grignard reagents. The method is characterized by the use of environmentally benign and sustainable iron salts for cross-coupling in the catalytic system, employing benign urea ligands in the place of reprotoxic NMP (NMP = N-methyl-2-pyrrolidone). It is notable that high selectivity for the cross-coupling is achieved in the presence of hydrolytically-labile and prone to nucleophilic addition phenolic ester C(acyl)-O bonds. The reaction provides access to alkyl-functionalized aryl benzoates. The examination of various O-coordinating ligands demonstrates the high activity of urea ligands in promoting the cross-coupling versus nucleophilic addition to the ester C(acyl)-O bond. The method showcases the functional group tolerance of iron-catalyzed Kumada cross-couplings.

Multifunctional Nanodroplets Encapsulating Naphthalocyanine and Perfluorohexane for Bimodal Image-Guided Therapy.

Although nanocarriers containing perfluorocarbon (PFC) have been widely investigated as an ultrasound (US) imaging agent and a high intensity focused ultrasound (HIFU) agent, these carriers have suffered from low stability and biocompatibility limiting their further biomedical applications. Here, we developed surface cross-linked polymer nanodroplets as a HIFU therapeutic agent guided by bimodal photoacoustic (PA) and US imaging. Pluronic F127 was reacted with 4-nitrophenyl chloroformate (NPC) and mixed with naphthalocyanine (Nc) in dichloromethane, which was added into the aqueous solution of amine-functionalized six-arm-branched poly(ethylene glycol) (PEG) to form an oil-in-water emulsion for the cross-linking reaction between the terminal NPC of Pluronic F127 and the primary amine of six-arm PEG. The resulting solution was sonicated with liquid perfluorohexane (PFH) to prepare PEG cross-linked Pluronic F127 nanoparticles encapsulating Nc and PFH (Nc/PFH@PCPN). Nc/PFH@PCPN appeared to be stable without any coalescence or vaporization in the physiological condition. Upon the application of HIFU, Nc/PFH@PCPN was vaporized and showed increased US intensity for 180 min. The Nc dye in the nanodroplets enabled the stable encapsulation of PFH and the bimodal US/PA imaging. In vivo PA/US image-guided HIFU ablation therapy confirmed that the nanodroplets increased the cavitation effect, induced necrosis and apoptosis of tumor cells, and reduced tumor growth significantly for 12 days. Taken together, the multifunctional Nc/PFH@PCPN was successfully developed as a new platform for PA/US image-guided HIFU therapy.

Regulators and mechanisms of anoikis in triple-negative breast cancer (TNBC): A review.

Metastasis leads to poor prognosis and reduced disease-free survival in breast cancer patients, particularly in those with triple-negative breast cancer (TNBC) which is resistant to common treatments. Anoikis is a type of apoptosis commenced by the detachment of cells from the native extracellular matrix and prohibits the attachment of detached cells to other body organs. Resistance to anoikis is a critical culprit in the development and progression of tumours. It is therefore important to understand the anoikis-related molecular pathways in order to design effective therapies for TNBC. Several compounds have been shown to possess the potential to regulate anoikis in breast cancer cells such as DSF, AEB071, nanoencapsulated doxorubicin, berberine, salinomycin, PEM POL5551, AL10, 5-azacytidine, synthesized flavonoid derivative GL-V9, Tubeimoside V (TBMS-V) and HPW-RX40. We reviewed the molecular basis of anoikis regulation, its potential role as an important target to inhibit metastasis in TNBC, and potential anoikis modulators that could serve as drug candidates.

Early embryonic exposure of ionizing radiations disrupts zebrafish pigmentation.

Studies have demonstrated that zebrafish are powerful tools for monitoring environmental toxicity, including radiation hazard. Here we investigated the developmental toxicity of ionizing radiation (IR) in an in vivo embryonic zebrafish model. The effects of heavy ion (12 C6+ ), proton, and X-ray radiation on early zebrafish embryos were determined. A similar dose-dependent decrease in the hatch and survival rate of zebrafish embryos was observed after exposure to these irradiations. Exposure of zebrafish embryos to 1-4 Gy IR caused significant loss of pigmentation. Quantitative real-time reverse transcription polymerase chain reaction, western blot analysis, and in situ hybridization (ISH) experiment revealed that atp5α1 was markedly upregulated in irradiated zebrafish embryos. In addition, IR resulted in a rapid decrease in total adenosine triphosphate (ATP) generation. With dual functions of synthesizing or hydrolyzing ATP, ATP synthase regulated H+ transport crossing the mitochondrial inner. Administration of the mitochondrial ATP synthase inhibitor, oligomycin, partially restored pigmentation in irradiated zebrafish embryos, but the ATPase inhibitor, BTB06584, had no effect. Taken together, these results showed that IR exposure downregulated zebrafish pigmentation through regulation of H+ ion transport in mitochondria.

Low levels of iron enhance UV/H2O2 efficiency at neutral pH.

While the presence of iron is generally not seen as favorable for UV-based treatment systems due to lamp fouling and decreased UV transmittance, we show that low levels of iron can lead to improvements in the abatement of chemicals in the UV-hydrogen peroxide advanced oxidation process. The oxidation potential of an iron-assisted UV/H2O2 (UV254 + H2O2 + iron) process was evaluated at neutral pH using iron levels below USEPA secondary drinking water standards (<0.3 mg/L). Para-chlorobenzoic acid (pCBA) was used as a hydroxyl radical (HO) probe to quantify HO steady state concentrations. Compounds degraded by different mechanisms including, carbamazepine (CBZ, HO oxidation) and N-nitrosodimethylamine (NDMA, direct photolysis), were used to investigate the effect of iron on compound degradation for UV/H2O2 systems. The effects of iron species (Fe2+ and Fe3+), iron concentration (0-0.3 mg/L), H2O2 concentration (0-10 mg/L) and background water matrix (low-carbon tap (LCT) and well water) on HO production and compound removal were examined. Iron-assisted UV/H2O2 efficiency was most influenced by the target chemical and the water matrix. Added iron to UV/H2O2 was shown to increase the steady-state HO concentration by approximately 25% in all well water scenarios. While CBZ removal was unchanged by iron addition, 0.3 mg/L iron improved NDMA removal rates in both LCT and well water matrices by 15.1% and 4.6% respectively. Furthermore, the combination of UV/Fe without H2O2 was also shown to enhance NDMA removal when compared to UV photolysis alone indicating the presence of degradation pathways other than HO oxidation.

The response of soil Arthrobacter agilis lush13 to changing conditions: Transition between vegetative and dormant state.

This work was aimed at studying the response of soil non-spore-forming actinobacterial strain Arthrobacter agilis Lush 13 to changing natural conditions, such as nutrient availability and the presence of degradable and recalcitrant aliphatic and aromatic substrates. The A. agilis strain Lush13 was able to degrade octane, nonane, hexadecane, benzoate, phenol, and 2,3-, 2,4-, 2,5-, 2,6-dichlorophenols, but not grew on 3,4-dichlorophenol, 2,3,4-, 2,4,5-, 2,4,6-trichlorophenol (TCP), pentachlorophenol (PCP), 2-chlorobenzoate, 3-chlorobenzoate, 3,5-dichlorobenzoate, 2,4-dichlorobenzoate. Under growth-arresting conditions due to nitrogen- or multiple starvation or recalcitrant (non-utilizable) carbon source, the studied strain preserved viability for prolonged periods (4-24 months) due to transition to dormancy in the form of conglomerated small and ultrasmall cyst-like dormant cells (CLC). Dormant cells were shown to germinate rapidly (30 min or later) after removal of starvation stress, and this process was followed by breakdown of conglomerates with the eliberation and further division of small multiple actively growing daughter cells. Results of this study shed some light to adaptive capabilities of soil arthrobacters in pure and polluted environments.

Characterization of an anti-varicella-zoster virus compound that targets the portal protein encoded by ORF54.

An anti-varicella-zoster virus compound, a 5-chlorobenzo[b]thiophen derivative (45B5), was characterized. Its 50% effective concentration against the cell-free vaccine Oka strain and 50% cytotoxic concentration in human fibroblasts were 16.9 µM and more than 100 µM, respectively. Treatment with 45B5 decreased viral DNA synthesis and IE62 expression weakly but significantly. All 45B5-resistant viral clones isolated were found to have at least one mutation in ORF54 that encodes the portal protein. There were no effects on interaction between the portal and scaffold proteins. Thus, 45B5 may inhibit nuclear delivery of viral DNA.

Cytosolic Phospholipase A2α Promotes Pulmonary Inflammation and Systemic Disease during Streptococcus pneumoniae Infection.

Pulmonary infection by Streptococcus pneumoniae is characterized by a robust alveolar infiltration of neutrophils (polymorphonuclear cells [PMNs]) that can promote systemic spread of the infection if not resolved. We previously showed that 12-lipoxygenase (12-LOX), which is required to generate the PMN chemoattractant hepoxilin A3 (HXA3) from arachidonic acid (AA), promotes acute pulmonary inflammation and systemic infection after lung challenge with S. pneumoniae As phospholipase A2 (PLA2) promotes the release of AA, we investigated the role of PLA2 in local and systemic disease during S. pneumoniae infection. The group IVA cytosolic isoform of PLA2 (cPLA2α) was activated upon S. pneumoniae infection of cultured lung epithelial cells and was critical for AA release from membrane phospholipids. Pharmacological inhibition of this enzyme blocked S. pneumoniae-induced PMN transepithelial migration in vitro Genetic ablation of the cPLA2 isoform cPLA2α dramatically reduced lung inflammation in mice upon high-dose pulmonary challenge with S. pneumoniae The cPLA2α-deficient mice also suffered no bacteremia and survived a pulmonary challenge that was lethal to wild-type mice. Our data suggest that cPLA2α plays a crucial role in eliciting pulmonary inflammation during pneumococcal infection and is required for lethal systemic infection following S. pneumoniae lung challenge.

HPW-RX40 prevents human platelet activation by attenuating cell surface protein disulfide isomerases.

Protein disulfide isomerase (PDI) present at platelet surfaces has been considered to play an important role in the conformational change and activation of the integrin glycoprotein IIb/IIIa (GPIIb/IIIa) and thus enhances platelet aggregation. Growing evidences indicated that platelet surface PDI may serve as a potential target for developing of a new class of antithrombotic agents. In the present study, we investigated the effects of HPW-RX40, a chemical derivative of ß-nitrostyrene, on platelet activation and PDI activity. HPW-RX40 inhibited platelet aggregation, GPIIb/IIIa activation, and P-selectin expression in human platelets. Moreover, HPW-RX40 reduced thrombus formation in human whole blood under flow conditions, and protects mice from FeCl3-induced carotid artery occlusion. HPW-RX40 inhibited the activity of recombinant PDI family proteins (PDI, ERp57, and ERp5) as well as suppressed cell surface PDI activity of platelets in a reversible manner. Exogenous addition of PDI attenuated the inhibitory effect of HPW-RX40 on GPIIb/IIIa activation. Structure-based molecular docking simulations indicated that HPW-RX40 binds to the active site of PDI by forming hydrogen bonds. In addition, HPW-RX40 neither affected the cell viability nor induced endoplasmic reticulum stress in human cancer A549 and MDA-MB-231 cells. Taken together, our results suggest that HPW-RX40 is a reversible and non-cytotoxic PDI inhibitor with antiplatelet effects, and it may have a potential for development of novel antithrombotic agents.

Structural basis for the inhibition of AKR1B10 by the C3 brominated TTNPB derivative UVI2008.

UVI2008, a retinoic acid receptor (RAR) ß/γ agonist originated from C3 bromine addition to the parent RAR pan-agonist 4-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl]benzoic acid (TTNPB), is also a selective inhibitor of aldo-keto reductase family member 1B10 (AKR1B10). Thus, it might become a lead drug for the design of compounds targeting both activities, as an AKR1B10 inhibitor and RAR agonist, which could constitute a novel therapeutic approach against cancer and skin-related diseases. Herein, the X-ray structure of the methylated Lys125Arg/Val301Leu AKR1B10 (i.e. AKME2MU) holoenzyme in complex with UVI2008 was determined at 1.5 Å resolution, providing an explanation for UVI2008 selectivity against AKR1B10 (IC50 = 6.1 µM) over the closely related aldose reductase (AR, IC50 = 70 µM). The carboxylic acid group of UVI2008 is located in the anion-binding pocket, at hydrogen-bond distance of catalytically important residues Tyr49 and His111. The inhibitor bromine atom can only fit in the wider active site of AKR1B10, mainly because of the native Trp112 side-chain orientation, not possible in AR. In AKR1B10, Trp112 native conformation, and thus UVI2008 binding, is facilitated through interaction with Gln114. IC50 analysis of the corresponding Thr113Gln mutant in AR confirmed this hypothesis. The elucidation of the binding mode of UVI2008 to AKR1B10, along with the previous studies on the retinoid specificity of AKR1B10 and on the stilbene retinoid scaffold conforming UVI2008, could indeed be used to foster the drug design of bifunctional antiproliferative compounds.

Inactivation efficiency and mechanism of UV-TiO2 photocatalysis against murine norovirus using a solidified agar matrix.

Human norovirus (HuNoV) is the primary cause of viral gastroenteritis worldwide. Fresh blueberries are among high risk foods associated with norovirus related outbreaks. Therefore, it is important to assess intervention strategies to reduce the risk of foodborne illness. The disinfection efficiency of decontamination methods is difficult to evaluate for fruits and vegetables due to an inconsistent degree of contamination and irregular surface characteristics. The inactivation efficiency and mechanism of murine norovirus 1 (MNV-1, a surrogate for HuNoV) was studied on an experimentally prepared solidified agar matrix (SAM) to simulate blueberries using different wavelengths (A, B, C) of UV light both with and without TiO2 photocatalysis (TP). MNV-1 was inoculated on exterior and interior of SAM and inactivation efficiencies of different treatments were investigated using a number of assays. Initial inoculum levels of MNV-1 on the SAM surface and interior were 5.2logPFU/mL. UVC with TiO2 (UVC-TP) achieved the highest level of viral reduction for both externally inoculated and internalized MNV-1. Externally inoculated MNV-1 was reduced to non-detectable levels after UVC-TP treatment for 5min while there was still a 0.9 log viral titer after UVC alone. For internalized MNV-1, 3.2 log and 2.7 log reductions were obtained with UVC-TP and UVC alone treatments for 10min, respectively. The Weibull model was applied to describe the inactivation behavior of MNV-1, and the model showed a good fit to the data. An excellent correlation between the steady-state concentration of OH radicals ([OH]ss) and viral inactivation was quantified using a para-chlorobenzoic acid (pCBA) probe compound, suggesting that OH radicals produced in the UV-TP reaction were the major species for MNV-1 inactivation. Transmission electron microscopy images showed that the structure of viral particles was completely disrupted with UVC-TP and UVC alone. SDS-PAGE analysis showed that the major capsid protein VP1 was degraded after UVC-TP and UVC alone. Real-time RT-qPCR analysis showed that UVC-TP and UVC alone caused a reduction in the level of viral genomic RNA. Propidium monoazide (PMA) pretreatment RT-qPCR analysis showed that UVC-TP caused damage to the viral capsid protein in addition to viral genomic RNA. UVC both with and without TiO2 was more effective for MNV-1 inactivation than UVB and UVA. Thus, UVC-TP disinfection aimed to reduce levels of food-borne viruses can inactivate viruses present on the surface and internalized in the interior of blueberries.

Detoxification of hydroxylated polychlorobiphenyls by Sphingomonas sp. strain N-9 isolated from forest soil.

To examine the biodegradation of hydroxylated polychlorobiphenyls (OH-PCBs), we isolated Sphingomonas sp. strain N-9 from forest soil using mineral salt medium containing 4-hydroxy-3-chlorobiphenyl (4OH-3CB) at the concentration of 10 mg/L. Following incubation with strain N-9, the concentration of 4OH-3CB decreased in inverse proportion to strain N-9 proliferation, and it was converted to 3-chloro-4-hydroxybenzoic acid (4OH-3CBA) after 1 day. We observed that strain N-9 efficiently degraded lowly chlorinated OH-PCBs (1-4 Cl), while highly chlorinated OH-PCBs (5-6 Cl) were less efficiently transformed. Additionally, strain N-9 degraded PCBs and OH-PCBs with similar efficiencies, and the efficiency of OH-PCB degradation was dependent upon the positional relationships between OH-PCB hydroxyl groups and chlorinated rings. OH-PCB biodegradation may result in highly toxic products, therefore, we evaluated the cytotoxicity of two OH-PCBs [4OH-3CB and 4-hydroxy-3,5-dichlorobiphenyl (4OH-3,5CB)] and their metabolites [4OH-3CBA and 3,5-chloro-4-hydroxybenzoic acid (4OH-3,5CBA)] using PC12 rat pheochromocytoma cells. Our results revealed that both OH-PCBs induced cell membrane damage and caused neuron-like elongations in a dose-dependent manner, while similar results were not observed for their metabolites. These results indicated that strain N-9 can convert OH-PCBs into chloro-hydroxybenzoic acids having lower toxicity.

Solution-phase microwave assisted parallel synthesis, biological evaluation and in silico docking studies of N,N'-disubstituted thioureas derived from 3-chlorobenzoic acid.

A facile and robust microwave-assisted solution phase parallel synthesis protocol was exercised for the development of a 38-member library of N,N'-disubstituted thiourea analogues (1-38) by using an identical set of conditions. The reaction time for synthesis of N,N'-disubstituted thiourea analogues was drastically reduced from a reported duration of 8-12h for conventional methods to only 1.5-2.0min. All the derivatives (1-38) were characterized by physico-analytical techniques such as elemental analysis in combination with FT-IR, (1)H, (13)C NMR and by single crystal XRD analysis have also been performed. These compounds were screened for their in vitro urease inhibition activities. Majority of compounds exhibited potent urease inhibition activities, however, the most significant activity was found for 16, with an IC50 value of 1.23±0.1µM. Furthermore, the synthesized compounds were screened for their cytotoxic potential against lungs cancer cell lines. Cell culture studies demonstrated significant toxicity of the compounds on the cell lines, and the levels of toxicity were altered in the presence of various side groups. The molecular docking studies of the most potent inhibitors were performed to identify the probable binding modes in the active site of the urease enzymes. These compounds have a great potential and significance for further investigations.