Sulfur-containing Derivatives Research Articles

Integrating UPLC-QTOF-MS/MS and UPLC-DAD to evaluate the influence of sulfur-fumigated Paeoniae Radix Alba on the overall quality of three Si-Wu-Tang formulations.

Sulfur-fumigation of Paeoniae Radix Alba (PRA) could induce the chemical transformation of its bioactive component paeoniflorin into a sulfur-containing derivative paeoniflorin sulfite, and thus alter the quality, bioactivities, pharmacokinetics, and toxicities of PRA. However, how sulfur-fumigated PRA (S-PRA) affects the quality of PRA-containing complex preparations has not been intensively evaluated. We intend to evaluate the influence of S-PRA on the overall quality of three kinds of Si-Wu-Tang (SWT) formulations, i.e., decoction (SWT-D), granule (SWT-G), and mixture (SWT-M). AnUPLC-DAD multi-components quantification method was used to compare the transfer rates of paeoniflorin sulfite and other 10 bioactive components between S-PRA-containing and NS-PRA-containing SWT formulations. An UPLC-QTOF-MS/MS-based target metabolomics approach was applied to explore the differential sulfur-containing derivatives in S-PRA-containing SWT formulations. The transfer rates of paeoniflorin sulfite in three S-PRA-containing SWT formulations were all higher than 100%. Moreover, S-PRA also increased the transfer rate of 5-hydroxymethylfurfural, 1,2,3,4,6-O-pentagalloylglucose, whereas decreased that of paeoniflorin, albiflorin, and ferulic acid in three SWT formulations. Six pinane monoterpene glucoside sulfites originally identified in S-PRA, were also detectable in three S-PRA-containing SWT formulations. In addition, seven phenolic acid sulfites including (3Z)-6-sulfite-ligustilide, (3E)-6-sulfite-ligustilide, 6,8-disulfite-ligustilide, ferulic acid sulfite, neochlorogenic acid sulfite, chlorogenic acid sulfite, and angelicide sulfite (or isomer) were newly identified in these three S-PRA-containing formulations. S-PRA could differentially affect the transfer rate of paeoniflorin sulfite and other bioactive components during the preparation of three SWT formulations and subsequently the overall quality thereof.

Metals/bisulfite system involved generation of 24-sulfonic-25-ene ginsenoside Rg1, a potential quality control marker for sulfur-fumigated ginseng

Ginseng is a most popular health-promoting food with ginsenosides as its main bioactive ingredients. Illegal sulfur-fumigation causes ginsenosides convert to toxic sulfur-containing derivatives, and reduced the efficacy/safety of ginseng. 24-sulfo-25-ene ginsenoside Rg1 (25-ene SRg1), one of the sulfur-containing derivatives, is a potential quality control marker of fumigated ginseng, but with low accessibility owing to its unknown generation mechanism. In this study, metals/bisulfite system involved generation mechanism was investigated and verified. The generation of 25-ene SRg1 in sulfur-fumigated ginseng is that SO2, formed during sulfur-fumigation, reacted with water and ionized into HSO3−. On the one hand, under the metals/bisulfite system, HSO3− generates HSO5− and free radicals which converted ginsenoside Rg1 to 24,25-epoxide Rg1; on the other hand, as a nucleophilic group, HSO3− reacted with 24,25-epoxide Rg1 and further dehydrated to 25-ene SRg1. This study provided a technical support for the promotion of 25-ene SRg1 as the characteristic quality control marker of sulfur-fumigated ginseng.

Unveiling the Chemical Composition of Sulfur-Fumigated Herbs: A Triple Synthesis Approach Using UHPLC-LTQ-Orbitrap MS-A Case Study on Steroidal Saponins in Ophiopogonis Radix.

Ophiopogonis Radix (OR) is a traditional Chinese medicine. In recent years, in order to achieve the purpose of drying, bleaching, sterilizing and being antiseptic, improving appearance, and easy storage, people often use sulfur fumigation for its processing. However, changes in the chemical composition of medicinal herbs caused by sulfur fumigation can lead to the transformation and loss of potent substances. Therefore, the development of methods to rapidly reveal the chemical transformation of medicinal herbs induced by sulfur fumigation can guarantee the safe clinical use of medicines. In this study, a combined full scan-parent ions list-dynamic exclusion acquisition-diagnostic product ions analysis strategy based on UHPLC-LTQ-Orbitrap MS was proposed for the analysis of steroidal saponins and their transformed components in sulfur-fumigated Ophiopogonis Radix (SF-OR). Based on precise mass measurements, chromatographic behavior, neutral loss ions, and diagnostic product ions, 286 constituents were screened and identified from SF-OR, including 191 steroidal saponins and 95 sulfur-containing derivatives (sulfates or sulfites). The results indicated that the established strategy was a valuable and effective analytical tool for comprehensively characterizing the material basis of SF-OR, and also provided a basis for potential chemical changes in other sulfur-fumigated herbs.

Qualitative and quantitative analysis of the component variations of Raphani Semen during the stir-frying process and elucidation of transformation pathways of multiple components

Raphani Semen (RS) encompasses two distinct application forms in Chinese clinical practice: raw RS (RRS) and stir-fried RS (SRS). They exhibit divergent drug properties and effects, as described in traditional Chinese medicine theory known as “Sheng shu yi zhi, sheng sheng shu jiang”. The dissimilarity in RS's drug properties is intrinsically linked to alterations in its internal components during the stir-frying process. Previous studies have demonstrated that stir-frying renders myrosinase inactive, thereby preventing the enzymatic hydrolysis of glucosinolates in RS. However, the precise enzymatic hydrolysis pathway and products of glucosinolates remain unclear. Furthermore, it remains uncertain whether other components undergo changes influenced by endogenous enzymes. The objective of this study is to systematically analyze the chemical components disparities between RRS and SRS using high-performance liquid chromatography coupled with time-of-flight mass spectrometry (HPLC-TOF-MS). Additionally, it seeks to elucidate the potential transformation pathways of multiple components from an enzymatic hydrolysis perspective. We have developed a sensitive and efficient high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (HPLC-QQQ-MS) method for quantifying the content of 5 characteristic components, including glucoraphenin, sinapine thiocyanate, sulforaphene, sinapic acid, and 3′,6-disinapoylsucrose. Based on retention time and MS spectra, we have identified 19 characteristic components in both SRS and RRS, encompassing glucosinolates and sulfur-containing derivatives, oligosaccharide esters, and small-molecule phenolic acids. Notably, 18 of these components undergo changes during the enzymatic hydrolysis process, leading to the identification of 4 transformation pathways: glucoraphenin, 6-sinapoylglucoraphenin, 3′,6-disinapoylsucrose and β-D-(3,4-disinapoyl) furanofructosyl-α-D-(6-sinapisoyl) glucoside, along with 3′-O-sinapoyl-6-O-feruloylsucrose. Quantitative analysis reveals significant differences, including lower levels of glucoraphenin in RRS compared to SRS, higher sulforaphene and sinapic acid levels in RRS, while sinapine thiocyanate and 3′,6-disinapoylsucrose remain unchanged before and after stir-frying. The results of this study highlight distinct chemical compositions between RRS and SRS. Additionally, the method of characterization and content determination constructed in this paper has strong practical value and provides a useful approach for comprehensively evaluating the chemical composition and quality of RS.

Thiocarbonyl Derivatives of Natural Chlorins: Synthesis Using Lawesson's Reagent and a Study of Their Properties.

The development of sulfur-containing pharmaceutical compounds is important in the advancement of medicinal chemistry. Photosensitizers (PS) that acquire new properties upon incorporation of sulfur-containing groups or individual sulfur atoms into their structure are not neglected, either. In this work, a synthesis of sulfur-containing derivatives of natural chlorophyll a using Lawesson's reagent was optimized. Thiocarbonyl chlorins were shown to have a significant bathochromic shift in the absorption and fluorescence bands. The feasibility of functionalizing the thiocarbonyl group at the macrocycle periphery by formation of a Pt(II) metal complex in the chemotherapeutic agent cisplatin was shown. The chemical stability of the resulting conjugate in aqueous solution was studied, and it was found to possess a high cytotoxic activity against sarcoma S37 tumor cells that results from the combined photodynamic and chemotherapeutic effect on these cells.

Exploring the nephrotoxicity of sulfur-containing derivatives in sulfur-fumigated Panacis Quinquefolii Radix based on chemical profiling and untargeted metabolomics

Ethnopharmacological relevancePanacis Quinquefolii Radix (PQR) is often illegally sulfur fumigated to extend shelf life and improve appearance, but existing regulations of detecting SO2 residues do not accurately identify desulfurized sulfur-fumigated PQR (SF-PQR). Although sulfur-containing derivatives (SCDs) have been reported in some sulfur-fumigated herbs, there is a lack of research on the generation mechanisms and toxicity of SCDs. Our previous study reported the nephrotoxicity of SF-PQR, and there is an urgent necessity to illuminate the mechanism of toxicity as well as its association with SCDs. Aim of the studyTo investigate the transformation pattern of chemical components and SCDs in SF-PQR, and to disclose the linkage between SCDs and SF-PQR nephrotoxicity. Materials and methodsThe extracts of PQR (before and after SF) were detected by the UPLC-LTQ-Orbitrap-MS method, and SCDs were screened as quality markers (Q-markers). The composition of sulfur combustion products was examined by ion chromatography to exploit the conversion mechanism of SCDs. After administration of PQR extracts to mice for two weeks, serum was collected for GC-MS-based untargeted metabolomics study to mine for differential metabolites. The upstream genes were traced by network analysis to probe toxicity targets. Molecular docking was used to uncover the interactions between SCDs and the targets. ResultsThirty-three compounds were identified and 11 SCDs of saponins were screened, including four SO3 sulfonation products and five H2SO3 sulfonation products. Metabolomics study showed significant alterations in serum biochemistry of SF-PQR group, with substantial increases in fumarate and 2-heptanone content, and induced disturbances in glycerolipid metabolism and phenylalanine, tyrosine, and tryptophan biosynthesis in mice. Network analysis revealed that the key toxicity targets were DECR1, PLA2G1B, and CAT. Molecular docking indicated that SCDs had stable interaction forces with the above three toxicity targets. ConclusionSF-PQR caused kidney damage by affecting glycerolipid metabolism and phenylalanine, tyrosine, and tryptophan biosynthesis. Eleven SCDs were potential nephrotoxic substances and Q-markers for identifying SF-PQR. This study is the first to systematically elucidate the mechanism of SF-PQR-related nephrotoxicity, providing a robust basis for the construction of new quality control standards and a global prohibition of sulfur fumigation.

The Potential Implications of Hydrogen Sulfide in Aging and Age-Related Diseases through the Lens of Mitohormesis.

The growing increases in the global life expectancy and the incidence of chronic diseases as a direct consequence have highlighted a demand to develop effective strategies for promoting the health of the aging population. Understanding conserved mechanisms of aging across species is believed helpful for the development of approaches to delay the progression of aging and the onset of age-related diseases. Mitochondrial hormesis (or mitohormesis), which can be defined as an evolutionary-based adaptive response to low-level stress, is emerging as a promising paradigm in the field of anti-aging. Depending on the severity of the perceived stress, there are varying levels of hormetic response existing in the mitochondria called mitochondrial stress response. Hydrogen sulfide (H2S) is a volatile, flammable, and toxic gas, with a characteristic odor of rotten eggs. However, H2S is now recognized an important gaseous signaling molecule to both physiology and pathophysiology in biological systems. Recent studies that elucidate the importance of H2S as a therapeutic molecule has suggested its protective effects beyond the traditional understanding of its antioxidant properties. H2S can also be crucial for the activation of mitochondrial stress response, postulating a potential mechanism for combating aging and age-related diseases. Therefore, this review focuses on highlighting the involvement of H2S and its sulfur-containing derivatives in the induction of mitochondrial stress response, suggesting a novel possibility of mitohormesis through which this gaseous signaling molecule may promote the healthspan and lifespan of an organism.

Anticancer activity and QSAR study of sulfur-containing thiourea and sulfonamide derivatives

Sulfur-containing compounds are considered as attractive pharmacophores for discovery of new drugs regarding their versatile properties to interact with various biological targets. Quantitative structure-activity relationship (QSAR) modeling is one of well-recognized in silico tools for successful drug discovery. In this work, a set of 38 sulfur-containing derivatives (Types I–VI) were evaluated for their in vitro anticancer activities against 6 cancer cell lines. In vitro findings indicated that compound 13 was the most potent cytotoxic agent toward HuCCA-1 cell line (IC50 = 14.47 μM). Compound 14 exhibited the most potent activities against 3 investigated cell lines (i.e., HepG2, A549, and MDA-MB-231: IC50 range = 1.50–16.67 μM). Compound 10 showed the best activity for MOLT-3 (IC50 = 1.20 μM) whereas compound 22 was noted for T47D (IC50 = 7.10 μM). Subsequently, six QSAR models were built using multiple linear regression (MLR) algorithm. All constructed QSAR models provided reliable predictive performance (training sets: Rtr range = 0.8301–0.9636 and RMSEtr = 0.0666–0.2680; leave-one-out cross validation sets: RCV range = 0.7628–0.9290 and RMSECV = 0.0926–0.3188). From QSAR modeling, chemical properties such as mass, polarizability, electronegativity, van der Waals volume, octanol-water partition coefficient, as well as frequency/presence of C–N, F–F, and N–N bonds in the molecule are essential key predictors for anticancer activities of the compounds. In summary, a series of promising fluoro-thiourea derivatives (10, 13, 14, 22) were suggested as potential molecules for future development as anticancer agents. Key structure-activity knowledge obtained from the QSAR modeling was suggested to be advantageous for suggesting the effective rational design of the related sulfur-containing anticancer compounds with improved bioactivities and properties.

Discrimination of raw and sulfur-fumigated ginseng based on Fourier transform infrared spectroscopy coupled with chemometrics

Ginseng (Panax ginseng), as a tonic and functional food in many countries and regions for thousands of years, is often sulfur-fumigated (SF) for storage and protection. However, our previous study indicated sulfur-fumigation could transform ginsenosides, the active components of ginseng, into sulfur-containing derivatives and thus affect the quality and safety of ginseng. In this study, a rapid and efficient method in discrimination of non-fumigated (NF) and SF ginseng was developed using Fourier transform infrared (FT-IR) spectroscopy coupled with multivariate statistical analysis. A total of 240 batches of raw spectra were obtained from NF and SF ginseng by FT-IR spectroscopy. After excluding the outliers, the different performance of 3 spectral signal enhancing methods, 3 modeling evaluation methods, and 4 model evaluation indexes were compared. The results demonstrated the feasibility of using FT-IR spectroscopy between 3650 and 3200 cm−1 for the detection of sulfur-fumigation in ginseng. After sulfur fumigation, the peak areas in fingerprint and functional group area varied significantly. In addition, the parameters of back propagation artificial neural network (BP-ANN) evaluation model are the highest, its accuracy = 91.67%, precision = 89.29%, recall = 96.15%, and F1 = 92.59%. The error rates of 3 models were k-nearest neighbor algorithm (KNN) (25.00%) > logistic regression (LR) (16.67%) > BP-ANN (8.33%). It can be concluded that FT-IR spectroscopy combined with multivariate statistical analysis has great potential in rapid discrimination of NF and SF ginseng, which can provide a valuable reference for the quality and effectiveness of edible and medicinal application of ginseng.

Effects of sulfur-fumigated ginseng on the global quality of Si-Jun-Zi decoction, a traditional ginseng-containing multi-herb prescription, evaluated by metabolomics and glycomics strategies

Si-Jun-Zi decoction (SJZD) with ginseng as the principal medicinal herb is a traditional Chinese Medicine multi-herb prescription that commonly employed to treat colorectal cancer etc. Previous studies showed that nearly half of the commercial ginseng was sulfur-fumigated, one of the postharvest processing methods that commonly causes sulfur-dioxide (SO2) residue and chemical composition transformation in medical herbs. In this study, the effect of sulfur-fumigated ginseng on global quality of SJZD was evaluated by UPLC-QTOF-MS/MS based metabolomics and multiple chromatographic techniques based glycomics strategies. For non-saccharides components, sulfur-fumigated ginseng led to the emergence of sulfur-containing derivatives and alteration of saponins and flavonoids in SJZD. For saccharide components, sulfur-fumigated ginseng decreased the total contents and molecular weights of polysaccharides, changed the monosaccharide composition of polysaccharides, and increased the contents of oligosaccharides and free monosaccharides of SJZD. The alterations of SJZD were aggravated with the sulfur-fumigated content of ginseng. Those phenomena might be attributed to 1) sulfur-fumigation caused the generation of sulfur-containing derivatives in ginseng, which further transferred to SJZD, and 2) sulfur-fumigation caused the residue of SO2 in ginseng, which reduced the pH value and further changed the dissolution of saponins and flavonoids and accelerated the degradation of the polysaccharides to oligosaccharides and/or monosaccharides in SJZD. Furthermore, although storage reduced the SO2 residue in sulfur-fumigated ginseng, it couldn’t recover the alterations of chemical profiles in SJZD. In conclusion, sulfur-fumigated ginseng altered the global quality of SJZD, which promoted that extra attention must be paid during the application of herbal formulas that containing sulfur-fumigated herbs.

In English

The aim of the current study was to find changes in the structure and state of the surface of graphene oxide (GO) under the conditions of its reduction and modification by hetero atoms of nitrogen and amino acids. Reduction of GO was performed with hydrazine hydrate (R-GO), doping with nitrogen atoms - urea impregnation and subsequent heat treatment (N-GO), and the surface of GO was modified with sulfur-containing amino acid – L-cysteine by nucleophilic addition (L-GO). The samples obtained were characterized by analytical methods, such as Raman scattering, IR spectroscopy, TPD-mass-spectrometry, dynamic light scattering spectroscopy. The available Raman spectra indicate a defective structure of GO, reduction of GO leads to greater ordering of the structure in relation to GO, nitrating and modification by amino acid - to the opposite effect, a slight deterioration of the structural state. According to the results of IR spectroscopy, also confirmed by TPD-MS, GO has a large number of functional surface groups: (OH), (C=O), (C=C), (C-O-C), (CO-O-CO), (CH). Hydrazine reduction completely hydrophobizes the surface, in the IR spectra there is only a peak at ~ 1040 cm–1, which corresponds to CO-O-CO vibrations, with significantly reduced intensity, as well as bands at 2120 and 2300 cm–1, which indicate the aromatic nature of the samples and exist in all GO derivatives. In nitrogen and sulfur-containing samples (L-GO) a new peak of ~ 1520 cm–1appears, which corresponds to N-H vibrations in amines. Sulfur-containing derivatives have valence vibrations at 600 cm–1, which most likely corresponds to S-H bonds. Thus, modification of GO leads to a significant change in its structure and surface chemistry, which in turn affects the capability of the obtained samples to capture free radicals. Previous empirical studies have shown that this property increases in the series L-GO > GO > N-GO > R-GO.

Effects and contributory factors of sulfur-fumigation on the efficacy and safety of medicinal herbs evaluated by meta-analysis

Ethnopharmacological relevanceSulfur-fumigation undoubtedly alters the chemical and metabolic profiles, but controversially affects the efficacy and safety of medicinal herbs. Aim of the studyTo comprehensively evaluate the effects of sulfur-fumigation on the efficacy and safety of medicinal herbs using a meta-analysis approach and further investigate the potential contributory factors. Materials and methodsLiteratures were retrieved on PubMed, Web of Science, Embase, China National Knowledge Infrastructure, Chinese VIP Information and Wanfang, and the outcomes involved activities and toxicities were extracted using standard data extraction forms. The effects of sulfur-fumigation on the efficacy and safety of medicinal herbs were evaluated by meta-analysis approaches. ResultsA total of sixteen studies were included in this study. Sulfur-fumigation reduced the efficacies of medicinal herbs with immune activity [thymus index (SMD = −1.81; P < 0.00001); spleen index (SMD = −1.11; P < 0.0001)], anti-oxidative activity [MDA (SMD = 2.60; P = 0.04); SOD (SMD = −2.21; P < 0.00001)], analgesic activity [heat tolerate time (SMD = −2.51; P = 0.001); writhing time (SMD = 0.36; P = 0.006)], anti-platelet aggregation activity (SMD = −1.84; P = 0.001), and anti-inflammatory activity [ear swelling degree (SMD = 0.47; P = 0.006)]. The reductions might be ascribed to sulfur-fumigation significantly reduced the contents of active ingredients in medicinal herbs, leading to dramatic decrease in the absorption of these ingredients and their metabolites in vivo. Furthermore, sulfur-fumigation induced the toxicities of medicinal herbs, mainly on hepatotoxicity, which might due to fumigation-induced residues of sulfur dioxide and heavy metal, and generations of sulfur-containing derivatives and toxic metabolites. Besides, administrated with sulfur-fumigated medicinal herbs with high sulfur ratio and/or higher dosage showed more significant toxicity. ConclusionSulfur-fumigation reduced the efficacy and safety of medicinal herbs, indicating sulfur-fumigation might not a feasible approach to process medicinal herbs. However, with obvious limitations, much more rigorous designed-trials are still needed to confirm the conclusion.

The antioxidant defense responses of Hordeum vulgare L. to polycyclic aromatic hydrocarbons and their derivatives in biochar-amended soil

The recent studies indicated that the biochar (BC) may be a source of polycyclic aromatic hydrocarbons (PAHs) as well as their oxygen, nitrogen, or sulfur-containing derivatives that are considered as more toxic pollutants than their parent compounds. Here, the assessment of the impact of various biochars addition (1% wt.) to soil on barley Hordeum vulgare L. growth was presented. The concentrations of bioavailable PAHs and their derivatives in biochar were determined. PAHs increased reactive oxygen species generation resulting in oxidative stress in organisms. In this study, the response of soil-grown plants was examined in terms of the activity of the antioxidative enzymes (superoxide dismutase, catalase, peroxidase), lipid peroxidation, and the expression of genes related to oxidative stress. The results indicate that despite low content of a bioavailable fraction of parent compounds and their derivatives (up to 4.45 ± 0.24 ng gbiochar−1 and 0.83 ± 0.03 ng L−1, respectively) the biochemical response of plant was present, the activity of superoxide dismutase increased up to 2 times, but the activity of the other enzymes was lowered. The transcript level values support the studies on enzymatic activity. The presence of PAHs and their derivatives induced oxidative stress slightly but the plant was able to mitigate it.

Synthesis, structures, DFT calculations, and Hirshfeld surface analysis of sulfonium derivatives of the closo-decaborate anion [B10X9-cyclo-S(CH2)4]– and [B10X9-cyclo-S(CH2CH2)2O]– (X = H, Cl, Br)

This work is devoted to the synthesis and modification of sulfur-containing derivatives of the closo-decaborate anion with cyclic substituents [2–B10H9–cyclo–S(CH2)4]–(1) and [2–B10H9-cyclo-S(CH2CH2)2O]–(2). Their perhalogenated analogs [2–B10Cl9–cyclo–S(CH2)4]–(3), [2–B10Cl9-cyclo-S(CH2CH2)2O]–(4), [2–B10Br9–cyclo–S(CH2)4]–(5), and [2–B10Br9-cyclo-S(CH2CH2)2O]–(6) were synthesized. The obtained compounds were investigated by 11B, 1H, and 13C NMR spectroscopy and single crystal X-ray diffraction. The analysis of Hirshfeld surfaces and quantum-chemical calculations by the DFT method made it possible to establish the contribution of various intermolecular contacts to the crystal packing of compounds 1–6 and to study the effect of substitution of hydrogen atoms in the boron cage on the strength of the B–S bond.

Dispirooxindoles Based on 2-Selenoxo-Imidazolidin-4-Ones: Synthesis, Cytotoxicity and ROS Generation Ability.

A regio- and diastereoselective synthesis of two types of dispiro derivatives of 2-selenoxoimidazolidin-4-ones, differing in the position of the nitrogen atom in the central pyrrolidine ring of the spiro-fused system—namely, 2-selenoxodispiro[imidazolidine-4,3′-pyrrolidine-2′,3″-indoline]-2″,5-diones (5a-h) and 2-senenoxodispiro[imidazolidine-4,3′-pyrrolidine-4′,3″-indoline]-2″,5-diones (6a-m)—were developed based on a 1,3-dipolar cycloaddition of azomethine ylides generated from isatin and sarcosine or formaldehyde and sarcosine to 5-arylidene or 5-indolidene-2-selenoxo-tetrahydro-4H-imidazole-4-ones. Selenium-containing dispiro indolinones generally exhibit cytotoxic activity near to the activity of the corresponding oxygen and sulfur-containing derivatives. Compounds 5b, 5c, and 5e demonstrated considerable in vitro cytotoxicity in the 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) test (concentration of compounds that caused 50% death of cells (CC50) 7.6–8.7 μM) against the A549 cancer cell line with the VA13/A549 selectivity index 5.2–6.9; some compounds (5 and 6) increased the level of intracellular reactive oxygen species (ROS) in the experiment on A549 and PC3 cells using platinized carbon nanoelectrode. The tests for p53 activation for compounds 5 and 6 on the transcriptional reporter suggest that the investigated compounds can only have an indirect p53-dependent mechanism of action. For the compounds 5b, 6b, and 6l, the ROS generation may be one of the significant mechanisms of their cytotoxic action.

Highly Stable Silver(I) Complexes with Cyclen-Based Ligands Bearing Sulfide Arms: A Step Toward Silver-111 Labeled Radiopharmaceuticals.

With a half-life of 7.45 days, silver-111 (βmax 1.04 MeV, Eγ 245.4 keV [Iγ 1.24%], Eγ 342.1 keV [Iγ 6.7%]) is a promising candidate for targeted cancer therapy with β– emitters as well as for associated SPECT imaging. For its clinical use, the development of suitable ligands that form sufficiently stable Ag+-complexes in vivo is required. In this work, the following sulfur-containing derivatives of tetraazacyclododecane (cyclen) have been considered as potential chelators for silver-111: 1,4,7,10-tetrakis(2-(methylsulfanyl)ethyl)-1,4,7,10-tetraazacyclododecane (DO4S), (2S,5S,8S,11S)-2,5,8,11-tetramethyl-1,4,7,10-tetrakis(2-(methylsulfanyl)ethyl)-1,4,7,10-tetraazacyclododecane (DO4S4Me), 1,4,7-tris(2-(methylsulfanyl)ethyl)-1,4,7,10-tetraazacyclododecane (DO3S), 1,4,7-tris(2-(methylsulfanyl)ethyl)-10-acetamido-1,4,7,10-tetraazacyclododecane (DO3SAm), and 1,7-bis(2-(methylsulfanyl)ethyl)-4,10,diacetic acid-1,4,7,10-tetraazacyclododecane (DO2A2S). Natural Ag+ was used in pH/Ag-potentiometric and UV–vis spectrophotometric studies to determine the metal speciation existing in aqueous NaNO3 0.15 M at 25 °C and the equilibrium constants of the complexes, whereas NMR and DFT calculations gave structural insights. Overall results indicated that sulfide pendant arms coordinate Ag+ allowing the formation of very stable complexes, both at acidic and physiological pH. Furthermore, radiolabeling, stability in saline phosphate buffer, and metal-competition experiments using the two ligands forming the strongest complexes, DO4S and DO4S4Me, were carried out with [111Ag]Ag+ and promising results were obtained.

Effect of sulfur-fumigation process on ginseng: Metabolism and absorption evidences

Ethnopharmacological relevanceSulfur-fumigation has been developed to prevent insects and molds during post-harvest handling of Panax ginseng C.A. Mey (ginseng) in the near decades. Our previous study indicated sulfur-fumigation could transform ginsenosides, the active components of ginseng, into sulfur-containing derivatives (SFCDs), the artifacts with unknown toxicity. However, whether the biotransformation could be occurred and absorption characteristics between ginsenosides and SFCDs are still needed to further investigate. Aim of the studyTo evaluate the effect of sulfur-fumigation process on ginseng through comparing the metabolic profile and absorption characteristics between ginsenoside Rg1, Re and their SFCDs. Materials and methodsIntestinal microflora and liver S9 fraction were utilized to compare the metabolic profile, and single-pass intestinal perfusion and Caco-2 cell models were applied to compare the absorption characteristics, between Rg1, Re and their SFCDs. ResultsRg1 and Re were metabolized to 7 none sulfur-containing metabolites, while their SFCDs were metabolized to 18 sulfur-containing metabolites. The intestinal absorption and transport of Rg1 and Re were much greater than their SFCDs. Besides, the uptakes of Rg1 and Re were transport-dependent, but their SFCDs were non-transport-dependent. ConclusionGinsenosides and their SFCDs could not be bio-transformed with each other and their absorption characteristics were quite different, which suggested that sulfur-fumigation is not a feasible post-harvest process of ginseng.

Comprehensive analysis of the chemical constituents in sulfur-fumigated Lonicerae Japonicae Flos using UHPLC-LTQ-Orbitrap mass spectrometry.

Lonicerae Japonicae Flos (LJF), a kind of traditional Chinese medicines (TCMs), has functions of detoxifying and evacuating heat. In the study, a method based on ultra-high performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap MS) was developed for the chemical constituent analysis of organic acids, flavonoids, iridoids and new-generated compounds in sulfur-fumigated LJF (SF-LJF). Based on the accurate mass measurement (< ± 5 ppm), chromatographic behavior and diagnostic product ions (DPIs), 113 constituents were unambiguously or tentatively characterized from SF-LJF extract, including 46 chlorogenic acids, 19 flavonoids, 29 iridoid glycosides and 19 newly-generated compounds (including 17 sulfur-containing derivatives). In addition, 5-CQA (5-caffeoylquinic acid, chlorogenic acid) was chosen to be sulfur-fumigated for the result validation. It was found that the most significant change of LJF after sulfur fumigation was the occurrence of sulfate or sulfite esterification reactions, which resulted in the emergence of many new sulfur-containing components. Our results demonstrated that the established method was a useful and efficient analytical tool to comprehensively characterize the material basis of SF-LJF, and also an excellent guidance of quality control about LJF.

Synthesis of Sulfur-Containing Cymantrene Derivatives Having Potential Photo- and Electrochemical Properties

With the aim of preparing of sulfur-containing derivatives of cymantrene, the hydrolysis of isothiouronium salts of alkylcymantrenes was studied under various conditions as well as subsequent chemical transformations of hydrolysis products. It was found that alkylcymantrenylthiols can be prepared either by hydrolysis of isothiouronium salts under the action of NaOH in a EtOH-acetone (4 : 1) mixture for 2 h or by the reduction of the corresponding disulfides by LiAlH4 formed in the course of this reaction in good yield for 6 h. Electrochemical properties of disulfides Cym(CHCH3)SS(CHCH3)Cym (Cym = C5H4Mn(CO)3) in solution before and after irradiation with a Hg lamp at λ365 nm were studied. The structures of the compounds were established by the X-ray analysis (CymCH(CH3)SSCH(CH3)Cym (I) (CIF file CCDC no. 1921952) and CymCH2SCH2Cym (II) (CIF file CCDC no. 1921953)).

Thionization Method of Glycosyl Urea and Carbamide Sugars

This work is describing a thionization method for glycosyl urea and carbamide of sugars by using the Lawesson’s reagent. It is proposed the method based on the interaction of glycosyl urea and carbamide of sugars with the Lawessons reagent at a 1:1 ratio in the presence of a pyridine. As a result, sulfur-containing derivatives of sugar carbamides are obtained with the help of Lawesson’s reagent. Obtained experimental data are indicating the developed new method for thionization of sugar carbamides, which opens up broad possibilities for synthesis of various carbohydrate derivatives of thiourea. Significance of this work is that, thiourea derivatives are promising bactericidal, fungicidal and anti-inflammatory drugs. Therefore, the preparation of thiourea derivatives and the study of their properties remain topical tasks in the field of chemistry.