Effective degradation of bentazone by two-dimensional and three-phase, three-dimensional electro-oxidation system: kinetic studies and optimization using ANN.

Bentazone is a broad-leaved weed-specific herbicide in the pesticide industry. This study focused on removing bentazone from water using three different methods: a two and three-dimensional electro-oxidation process (2D/EOP and 3D/EOP) with a fluid-type reactor arrangement using tetraethylenepentamine-loaded particle electrodes and an adsorption method. Additionally, we analysed the effects of two types of supporting electrolytes  (Na2SO4 and NaCl) on the degradation process. The energy consumption amounts were calculated to evaluate the obtained results. The degradation reaction occurs 3.5 times faster in 3D/EOP than in 2D/EOP at 6 V in Na2SO4. Similarly, the degradation reaction of bentazone in NaCl occurs 2.5 times faster in 3D/EOP than in 2D/EOP at a value of 7.2 mA/cm2. Removal of bentazone is significantly better in 3D/EOPs than in 2D/EOPs. The use of particle electrodes can significantly enhance the degradation efficiency. The study further assessed the prediction abilities of the machine learning model (ANN). The ANN presented reasonable accuracy in bentazone degradation with high R2 values of 0.97953, 0.98561, 0.98563, and 0.99649 for 2D with Na2SO4, 2D with NaCl, 3D with Na2SO4, and 3D with NaCl, respectively.

New insights in the development of positive allosteric modulators of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors belonging to 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides: Introduction of (mono/difluoro)methyl groups at the 2-position of the thiadiazine ring.

Positive allosteric modulators of the AMPA receptors (AMPAR PAMs) have been proposed as new drugs for the management of various neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, attention deficit hyperactivity disorder, depression, and schizophrenia. The present study explored new AMPAR PAMs belonging to 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides (BTDs) characterized by the presence of a short alkyl substituent at the 2-position of the heterocycle and by the presence or absence of a methyl group at the 3-position. The introduction of a monofluoromethyl or a difluoromethyl side chain at the 2-position instead of the methyl group was examined. 7-Chloro-4-cyclopropyl-2-fluoromethyl-3,4-dihydro-4H-1,2,4-benzothiadiazine 1,1-dioxide (15e) emerged as the most promising compound associating high in vitro potency on AMPA receptors, a favorable safety profile in vivo and a marked efficacy as a cognitive enhancer after oral administration in mice. Stability studies in aqueous medium suggested that 15e could be considered, at least in part, as a precursor of the corresponding 2-hydroxymethyl-substituted analogue and the known AMPAR modulator 7-chloro-4-cyclopropyl-3,4-dihydro-4H-1,2,4-benzothiadiazine 1,1-dioxide (3) devoid of an alkyl group at the 2-position.

Design, Synthesis, and Evaluation of Novel Pyruvate Dehydrogenase Kinase Inhibitors.

AIMS: The present work describes the synthesis and the biological evaluation of novel compounds acting as pyruvate dehydrogenase kinase (PDK) inhibitors. These drugs should become a new therapeutic approach for the treatment of pathologies improved by the control of the blood lactate level. METHODS: Four series of compounds belonging to N-(4-(N-alkyl/aralkylsulfamoyl)phenyl)-2- methylpropanamides and 1,2,4-benzothiadiazine 1,1-dioxides were prepared and evaluated as PDK inhibitors. RESULTS: The newly synthesized N-(4-(N-alkyl/aralkylsulfamoyl)phenyl)-2-methylpropanamides structurally related to previously reported reference compounds 4 and 5 were found to be potent PDK inhibitors (i.e. 10d: IC50 = 41 nM). 1,2,4-Benzothiadiazine 1,1-dioxides carrying a (methyl/ trifluoromethyl)-propanamide moiety at the 6-position were also designed as conformationally restricted ring-closed analogues of N-(4-(N-alkyl/aralkylsulfamoyl)phenyl)-2-hydroxy-2-methylpropanamides. Most of them were found to be less potent than their ring-opened analogues. Interestingly, the best choice of hydrocarbon side chain at the 4-position was the benzyl chain, providing 11c (IC50 = 3.6 µM) belonging to "unsaturated" 1,2,4-benzothiadiazine 1,1-dioxides, and 12c (IC50 = 0.5 µM) belonging to "saturated' 1,2,4-benzothiadiazine 1,1-dioxides. CONCLUSION: This work showed that ring-closed analogues of N-(4-(N-alkyl/aralkylsulfamoyl) phenyl)- 2-hydroxy-2-methylpropanamides were less active as PDK inhibitors than their corresponding ring-opened analogues. However, the introduction of a bulkier substituent at the 4-position of the 1,2,4-benzothiadiazine 1,1-dioxide core structure, such as a benzyl or a phenethyl side chain, was allowed, opening the way to the design of new inhibitors with improved PDK inhibitory activity.

Cobalt(III)/Chiral Carboxylic Acid-Catalyzed Enantioselective Synthesis of Benzothiadiazine-1-oxides via C-H Activation.

Among sulfoximine derivatives containing a chiral sulfur center, benzothiadiazine-1-oxides are important for applications in medicinal chemistry. Here, we report that the combination of an achiral cobalt(III) catalyst and a pseudo-C2 -symmetric H8 -binaphthyl chiral carboxylic acid enables the asymmetric synthesis of benzothiadiazine-1-oxides from sulfoximines and dioxazolones via enantioselective C-H bond cleavage. With the optimized protocol, benzothiadiazine-1-oxides with several functional groups can be accessed with high enantioselectivity.

Structure of benzothiadiazine at zwitterionic phospholipid cell membranes.

The use of drugs derived from benzothiadiazine, which is a bicyclic heterocyclic benzene derivative, has become a widespread treatment for diseases such as hypertension (treated with diuretics such as bendroflumethiazide or chlorothiazide), low blood sugar (treated with non-diuretic diazoxide), or the human immunodeficiency virus, among others. In this work, we have investigated the interactions of benzothiadiazine with the basic components of cell membranes and solvents, such as phospholipids, cholesterol, ions, and water. The analysis of the mutual microscopic interactions is of central importance to elucidate the local structure of benzothiadiazine as well as the mechanisms responsible for the access of benzothiadiazine to the interior of the cell. We have performed molecular dynamics simulations of benzothiadiazine embedded in three different model zwitterionic bilayer membranes made by dimyristoylphosphatidylcholine, dioleoylphosphatidylcholine, 1,2-dioleoyl-sn-glycero-3-phosphoserine, and cholesterol inside aqueous sodium-chloride solution in order to systematically examine microscopic interactions of benzothiadiazine with the cell membrane at liquid-crystalline phase conditions. From data obtained through radial distribution functions, hydrogen-bonding lengths, and potentials of mean force based on reversible work calculations, we have observed that benzothiadiazine has a strong affinity to stay at the cell membrane interface although it can be fully solvated by water in short periods of time. Furthermore, benzothiadiazine is able to bind lipids and cholesterol chains by means of single and double hydrogen-bonds of different characteristic lengths.

Synthesis and in vitro antileishmanial efficacy of novel benzothiadiazine-1,1-dioxide derivatives.

Leishmaniasis is a major vector-borne parasitic disease that affects thousands of people in tropical and subtropical developing countries. In 2019 alone, it killed 26,000-65,000 individuals. Leishmaniasis is curable, yet its eradication and elimination are hampered by major hurdles, such as the availability of only a handful of clinical toxic drugs and the emergence of pathogenic resistance against them. This underscores the imperative need for new and effective antileishmanial drugs. In search for such agents, we synthesized and evaluated the in vitro antileishmanial potential of a small library of benzothiadiazine derivatives by assessing their activity against the promastigotes of three strains of Leishmania and toxicity in healthy cells. The derivatives were found to have no toxicity to the mammalian cells and were, in general, active against all parasites. The benzothiadiazine derivative 1e, 3-methyl-2-[3-(trifluoromethyl)benzyl]-2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide, was found to be the most active (IC50 , 0.2 µM) against Leishmania major, responsible for the most prevalent disease form, cutaneous leishmaniasis. Conversely, benzothiadiazine 2c, 2-(4-bromobenzyl)-3-phenyl-2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide, was the most potent (IC50 , 6.5 µM) against Leishmania donovani, a causative strain of the lethal visceral leishmaniasis. Both compounds stand as antipromastigote hits for further lead investigation into their potential to act as new antileishmanial agents.

Discovery of Halogenated Benzothiadiazine Derivatives with Anticancer Activity*.

Mitochondrial respiratory complex II (CII), also known as succinate dehydrogenase, plays a critical role in mitochondrial metabolism. Known but low potency CII inhibitors are selectively cytotoxic to cancer cells including the benzothiadiazine-based anti-hypoglycemic diazoxide. Herein, we study the structure-activity relationship of benzothiadiazine derivatives for CII inhibition and their effect on cancer cells for the first time. A 15-fold increase in CII inhibition was achieved over diazoxide, albeit with micromolar IC50 values. Cytotoxicity evaluation of the novel derivatives resulted in the identification of compounds with much greater antineoplastic effect than diazoxide, the most potent of which possesses an IC50 of 2.93±0.07 µM in a cellular model of triple-negative breast cancer, with high selectivity over nonmalignant cells and more than double the potency of the clinical agent 5-fluorouracil. No correlation between cytotoxicity and CII inhibition was found, thus indicating an as-yet-undefined mechanism of action of this scaffold. The derivatives described herein represent valuable hit compounds for therapeutic discovery in triple-negative breast cancer.

Adsorption of bentazone in the profiles of mineral soils with low organic matter content.

The current laboratory adsorption study aimed at determination of the values of adsorption distribution coefficient (Kd) of bentazone in the profiles of Arenosols, Luvisols, and Cambisols, which are the most common arable mineral soils in Poland. The study attempted to identify the soil components that bind bentazone and the principal adsorption mechanisms of this compound as well as create a model capable of predicting its adsorption in soils. The Kd values determined in batch experiments after 24 h of shaking were very low, and ranged from 0.05 to 0.30 mL/g for the Ap horizon and 0 to 0.07 mL/g for subsoils. The results indicated that the anionic form of bentazone was adsorbed on organic matter, while in acidic soils the neutral form of bentazone was adsorbed on organic matter and sand. The detailed analyses of mineralogical composition revealed that the principal mineral that was responsible for the adsorption of bentazone was quartz, which content was strongly positively correlated with the sand fraction. In soils with pH < 5 and an organic carbon content of < 0.35%, quartz exhibited much greater affinity for the neutral bentazone form than organic matter. Fourier transform infrared photoacoustic spectroscopy analyses supported by computational methods have shown the most probable mechanisms behind the adsorption of bentazone on quartz. The created model, assuming the adsorption of bentazone on organic matter and on sand and using the spectrophotometrically determined dissociation constant of bentazone, very well explained the Kd variance in the 81 examined soils, while correctly predicting the adsorption based on soil properties described in the published data.

Oxidative degradation and mineralization of bentazone from water.

Bentazone degradation efficiency and mineralization in water solutions using chlorine dioxide treatment were evaluated. Double distilled water and a river water sample spiked with bentazone were studied and compared after chlorine dioxide treatment. Degradation efficiency was determined using high-performance liquid chromatography (HPLC). Daphnia magna toxicity testing and total organic carbon (TOC) analysis were used to ascertain the toxicity of the degraded solutions and mineralization degree. Bentazone degradation products were identified using gas chromatography with a triple quadrupole mass detector (GC-MS-MS). A simple mechanistic scheme for oxidative degradation of bentazone was proposed based on the degradation products that were identified. Decrease in D. magna mortality, high degradation efficiency and partial bentazone mineralization were achieved by waters containing bentazone degradation products, which indicate the formation of less toxic compounds than the parent bentazone and effective removal of bentazone from the waters. Bentazone degraded into four main degradation products. Humic acid from Sava River water influenced bentazone degradation, resulting in a lower degradation efficiency in this matrix (about 10% lower than in distilled water). Chlorine dioxide treatment of water to degrade bentazone is efficient and offers a novel approach in the development of new technology for removal of this herbicide from contaminated water.

Amyloid Fibrils Aerogel for Sustainable Removal of Organic Contaminants from Water.

Water contamination by organic pollutants is ubiquitous and hence a global concern due to detrimental effects on the environment and human health. Here, it is demonstrated that amyloid fibrils aerogels are ideal adsorbers for removing organic pollutants from water. To this end, amyloid fibrils prepared from ß-lactoglobulin, the major constituent of milk whey protein, are used as building blocks for the fabrication of the aerogels. The adsorption of Bentazone, Bisphenol A, and Ibuprofen, as model pollutants, is evaluated under quasi-static conditions, without use of energy or pressure. Through adsorption by amyloid fibrils aerogel, excellent removal efficiencies of 92%, 78%, and 98% are demonstrated for Bentazone, Bisphenol A, and Ibuprofen, respectively. Furthermore, the maximum adsorption capacity of amyloid fibrils aerogel for Bentazone, Bisphenol A, and Ibuprofen is 54.2, 50.6, and 69.6 mg g-1 , respectively. To shed light on the adsorption equilibrium process, adsorption isotherms, binding constants, saturation limits, and the effect of pH are evaluated. Finally, the regeneration of the aerogel over three consecutive cycles is studied, exhibiting high reusability with no significant changes in its removal performance. These results point at amyloid fibrils aerogels as a sustainable, efficient, and inexpensive technology for alleviating the ubiquitous water contamination by organic pollutants.

The role of direct photolysis in the photodegradation of the herbicide bentazone in natural surface waters.

The photochemical fate of the herbicide bentazone was assessed by lab experiments and modeling tools. Experimental and modeling results showed that bentazone is mainly photodegraded by direct photolysis in natural water samples, even in the presence of dissolved organic matter (DOM) that can act as light-screening agent, photosensitizer and scavenger of reactive species. Even when it was dissolved in natural water samples containing different DOM amounts, the phototransformation kinetics of bentazone was unchanged compared to irradiation runs in ultrapure water. This finding suggests that the DOM and the other components of our samples did not affect the direct photolysis of bentazone by light-absorption competition, at least at the experimental optical path lengths, and did not induce significant indirect photodegradation by producing reactive transient species. Photochemical modeling in a lake-water photoreactivity scenario corroborated the observed experimental results, showing the predominant role of direct photolysis in the overall (direct + indirect) photodegradation of bentazone at different water depths and DOM contents. However, the model predicted a minor but non-negligible contribution of indirect photochemistry (i.e., reactions triggered by HO•, CO3•- and 3CDOM*) to the herbicide degradation. This contribution (especially by 3CDOM*) could become crucial in deep and DOM-rich water bodies. Finally, several photoproducts formed by direct photolysis and HO•-induced photodegradation were identified, which should not be particularly toxic for aquatic organisms and Vibrio fischeri bacteria.

Assembly of Benzothiazine and Triazole in a Single Molecular Entity: Synthesis of -Oxicam Derived Novel Molecules as Potential Antibacterial/ Anti-cancer Agents.

BACKGROUND: Benzothiazine derivatives, because of their various biological activities have attracted particular attention in Med Chem and drug discovery efforts. The synthetic modifications of 1,2-benzothiazine 1,1-dioxides have been undertaken in order to explore and identify novel compounds or new analogues possessing promising biological activities. In our effort we have designed -oxicam derived bezothiazine-1,2,3-triazole derivatives as potential antibacterial agents. METHODS: These compounds were synthesized via a multi-step sequence involving the Cu catalyzed azide- alkyne cycloaddition (CuAAC) as a key step. The CuAAC proceeded at room temperature in DMF to afford 26 novel molecules in good (70-90%) yields. RESULTS: All these compounds were tested for their antibacterial properties against four strains of bacterial microorganisms and subsequently cytotoxic properties against lung and colon cancer cell lines. The compound 4e showed activities against majority of the bacterial species used (nearly comparable to amoxicillin, ciprofloxacin and ofloxacin against P. vulgaris) whereas 4d and 4f showed cytotoxicities selective towards cancer cells. CONCLUSION: The present bezothiazine-1,2,3-triazole framework represents a new template for the identification of novel and potent antibacterial/anticancer agents.

Efficacy of biochar in removal of organic pesticide, Bentazone from watershed systems.

Bentazone is one of the toxic insecticides used to control forest tent caterpillar moths, boll weevils, gypsy moths, and other types of moths in various field crops. We report the efficacy of biochar prepared from the Azardirachta Indica waste biomass as adsorbent for removal of Bentazone. Biochar material was prepared by pyrolysis process under limited oxygen conditions. Biochar material was characterized by proximate and ultimate analysis, SEM analysis, FTIR analysis and TG/DTA analyses. The Bentazone adsorption capacity by biochar from aqueous solutions was assessed. Effect of time, adsorbent dosage, insecticide concentration and pH on the adsorption characteristics of the biochar were evaluated. Adsorption parameters were obtained at equilibrium contact time of 150 min, with biochar dosage of 0.5 g at pH 8. From the optimization studies, desirability of 0.952 was obtained with response (adsorption uptake) of 79.40 mg/g, for initial concentration of insecticide (50 mg/L), adsorbent dosage (0.448 g), time 30.0 min and pH 2. The adsorption isotherm data for the removal of Bentazone fitted well with the Freundlich isotherm. This study indicates that the biochar produced from the bark of Azardirachta Indica biomass could be employed as a potential adsorbent for removal of synthetic organic pollutants from the water streams.

Evaluation of Anticancer and Anti-Mitotic Properties of Quinazoline and Quinazolino-Benzothiadiazine Derivatives.

BACKGROUND: Cancer is one of the major health and social-economic problems despite considerable progress in its early diagnosis and treatment. Owing to the emergence and increase of multidrug resistance to various conventional drugs, and the continuing importance of health-care expenditure, many researchers have focused on developing novel and effective anticancer compounds. OBJECTIVE: Chemical repositories provide a good platform to evaluate and exploit known chemical entities for the identification of other biological activities. In the present study, we have selected an in-house library of synthesized compounds based on two different pharmacophoric scaffolds to evaluate their cytotoxic potency on various cancer cell lines and mechanisms of action. METHODS: A series of in-house synthesized quinazoline and quinazolino-benzothiadiazine derivatives were investigated for their anticancer efficacy against a panel of five cancer (DU145, MCF7, HepG2, SKOV3 and MDA-MB-231) and one normal (MRC5) cell lines. Furthermore, the active compound of the study was investigated to elucidate the mechanism of cytotoxicity by performing series of experiments such as cell cycle analysis, inhibition of tubulin polymerization, alteration of mitochondrial membrane potential, determination of endocytic pathway for drug uptake pathway and combination drug treatment. RESULTS: Among all the tested compounds, fifteen of them exhibited promising growth-inhibitory effect (0.15- 5.0µM) and induced cell cycle arrest in the G2/M phase. In addition, the selected compounds inhibited the microtubule assembly; altered mitochondrial membrane potential and enhanced the levels of caspase-9 in MCF-7 cells. Furthermore, the active compound with a combination of drugs showed a synergistic effect at lower concentrations, and the drug uptake was mediated through clathrin-mediated endocytic pathway. CONCLUSION: Our results indicated that quinazoline and quinazolino-benzothiadiazine conjugates could serve as potential leads in the development of new anticancer agents.

Dissipation of mecoprop-P, isoproturon, bentazon and S-metolachlor in heavy metal contaminated acidic and calcareous soil before and after EDTA-based remediation.

The ability of contaminated farmland soils reclaimed by remediation to dissipate pesticides and thus to mitigate their unwanted environmental effects, i.e., leaching and run-off, was studied. Novel EDTA-based soil washing technology (EDTA and process waters recycling; no toxic emissions) removed 79 and 73% of Pb from acidic and calcareous soil with 740 and 2179 mg kg-1 Pb, respectively. The dissipation kinetics of four herbicides: mecoprop-P, isoproturon, bentazon and S-metolachlor was investigated under field conditions in beds with maize (Zea mays) and barley (Hordeum vulgare). The biphasic First-Order Multi-Compartment (FOMC) model was used to fit experimental data and calculate the herbicides' half-life (DT50) in soil. Remediation significantly (up to 64%) decreased dehydrogenase activity assessed as a marker of soil microbial activity and prolonged the DT50 of herbicides in acidic soils from 16% (isoproturon) to 111% (S-metachlor). Remediation had a less significant effect on herbicide dissipation in calcareous soils; i.e., mecoprop-P DT50 increased by 3%, while isoproturon and S-metachlor DT50 decreased by 29%. Overall, the dissipation from remediated soils was faster than the average DT50 of tested herbicides published in the Pesticides Properties DataBase. Results demonstrate that EDTA-based remediation of the studied soils does not pose any threat of extended herbicide persistence.

Design, synthesis and biological evaluation of novel benzothiadiazine derivatives as potent PI3Kδ-selective inhibitors for treating B-cell-mediated malignancies.

A series of 24 benzothiadiazine derivatives with structural novelty were designed, synthesized and biologically evaluated as PI3Kδ-selective inhibitors. As a consequence of the structure-activity relationship (SAR) study, compounds 63 and 71 were identified with single-digit nanomolar IC50 values against PI3Kδ and submicromolar GI50 values against human malignant B-cell line SU-DHL-6. Furthermore, chiral resolution of the key amine intermediate of these two compounds was performed to achieve corresponding enantiomers. In subsequent biological evaluation, S-63 (IC50: 4.6 nM) and S-71 (IC50: below 0.32 nM) demonstrated comparable and superior PI3Kδ inhibitory activity, respectively, to that of idelalisib. Additionally, both S-63 (GI50: 33.2 nM) and S-71 (GI50: 15.9 nM) exerted enhanced anti-proliferative activity against the SU-DHL-6 cell line than that of idelalisib. Moreover, both S-63 and S-71 exhibited excellent PI3Kδ selectivity. In the further in vivo pharmacokinetic (PK) study, S-63 displayed a good plasma exposure and an acceptable oral bioavailability of 29.2%. By virtue of its biological performance, S-63 merits further development as a potential therapeutic agent for battling B-cell-mediated malignancies.

Isotopic tagging of oxidized and reduced cysteines (iTORC) for detecting and quantifying sulfenic acids, disulfides, and free thiols in cells.

Oxidative modifications of cysteine residues are an important component in signaling pathways, enzymatic regulation, and redox homeostasis. Current direct and indirect methods detect specific modifications and a general binary population of "free" or "oxidized" cysteines, respectively. In an effort to combine both direct and indirect detection strategies, here we developed a method that we designate isotopic tagging of oxidized and reduced cysteines (iTORC). This method uses synthetic molecules for rapid isotopic coding of sulfenic acids, reduced cysteines, and disulfides in cells. Our approach utilizes isotopically distinct benzothiazine and halogenated benzothiazine probes to sequentially alkylate sulfenic acids and then free thiols and, finally, after a reduction step, cysteines oxidized to disulfides or other phosphine-reducible states. We ascertained that the iodinated benzothiazine probe has reduced cross-reactivity toward primary amines and is highly reactive with the cysteine of GSH, with a calculated rate constant of 2 × 105 m-1 s-1 (pH 8.0, 23 °C) (i.e. 10-20 times faster than N-ethylmaleimide). We applied iTORC to a mouse hepatocyte lysate to identify known sulfenylated and disulfide-bonded proteins, including elongation factor 1-α1 and mouse serum albumin, and found that iTORC reliably detected their expected oxidation status. This method can be easily employed to study the effects of oxidants on recombinant proteins and cell and tissue extracts, and the efficiencies of the alkylating agents enable completion of all three labeling steps within 2 h. In summary, we demonstrate here that halogenated benzothiazine-based alkylating agents can be utilized to rapidly measure the cellular thiol status in cells.

Comparative Molecular Field Analysis and Molecular Docking Studies on Quinolinone Derivatives Indicate Potential Hepatitis C Virus Inhibitors.

Presently, there are no effective vaccines and anti-virals for the prevention and treatment of Hepatitis C virus infections and hence there is an urgent need to develop potent HCV inhibitors. In this study, we have carried out molecular docking, molecular dynamics and 3D-QSAR on heteroaryl 3-(1,1-dioxo-2H-(1,2,4)-benzothiadizin-3-yl)-4-hydroxy-2(1H)-quinolinone series using NS5B protein. Total of 41 quinolinone derivatives is used for molecular modeling study. The binding conformation and hydrogen bond interaction of the docked complexes were analyzed to model the inhibitors. We identified the molecule XXXV that had a higher affinity with NS5B. The molecular dynamics study confirmed the stability of the compound XXXV-NS5B complex. The developed CoMFA descriptors parameters, which were calculated using a test set of 13 compounds, were statistically significant. Our results will provide useful insights and lead to design potent anti-Hepatitis C virus molecules.

Hydrolysis and photolysis of bentazone in aqueous abiotic solutions and identification of its degradation products using quadrupole time-of-flight mass spectrometry.

Hydrolysis and photolysis of bentazone in abiotic aqueous solutions were examined under laboratory conditions. Hydrolysis was studied in different buffer solutions (pH 4.0 ± 0.1, 7.0 ± 0.1, and 9.0 ± 0.1), at different temperatures (15 °C ± 2 °C, 25 °C ± 2 °C, 35 °C ± 2 °C, and 45 °C ± 2 °C), and at different Fe3+ concentrations (1, 5, and 10 mg/L). Photolysis was assessed in different buffer solutions and at different solvent (methanol and ethyl acetate) concentrations (10%, 20%, and 30%) or Fe3+ (1, 5, and 10 mg/L) concentrations and under mercury or xenon light irradiation. Hydrolysis half-lives ranged 46-99 days at three different conditions. Photolysis half-lives ranged 2.3-7.5 h in three different conditions under mercury and xenon irradiation. Hydrolysis and photolysis of bentazone were accelerated by both alkaline conditions and elevated temperatures, and solvents and Fe3+ strongly enhanced bentazone degradation. Photodecomposition was much faster under a mercury lamp than under a xenon lamp. N-methyl bentazone and 6-OH bentazone/8-OH bentazone were identified as degradation products using UPLC-Q-TOF-MS. The data generated from this study could be useful for risk assessment of pesticides in the environment.

Proteome-Wide Analysis of Cysteine S-Sulfenylation Using a Benzothiazine-Based Probe.

Oxidation of a protein cysteinyl thiol (Cys-SH) to S-sulfenic acid (Cys-SOH) by a reactive oxygen species (e.g., hydrogen peroxide), which is termed protein S-sulfenylation, is a reversible post-translational modification that plays a crucial role in redox regulation of protein function in various biological processes. Due to its intrinsically labile nature, protein S-sulfenylation cannot be directly detected or analyzed. Chemoselective probing has been the method of choice for analyzing S-sulfenylated proteins either in vitro or in situ, as it allows stabilization and direct detection of this transient oxidative intermediate. However, it remains challenging to globally pinpoint the specific S-sulfenylated cysteine sites on complex proteomes and to quantify their dynamic changes upon oxidative stress. This unit describes how a benzothiazine-based chemoselective probe called BTD and mass spectrometry based chemoproteomics can be used to globally and site-specifically identify and quantify protein S-sulfenylation. © 2018 by John Wiley & Sons, Inc.