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Nature Chemistry Feb 2018Cyclic amines are ubiquitous core structures of bioactive natural products and pharmaceutical drugs. Although the site-selective abstraction of C-H bonds is an...
Cyclic amines are ubiquitous core structures of bioactive natural products and pharmaceutical drugs. Although the site-selective abstraction of C-H bonds is an attractive strategy for preparing valuable functionalized amines from their readily available parent heterocycles, this approach has largely been limited to substrates that require protection of the amine nitrogen atom. In addition, most methods rely on transition metals and are incompatible with the presence of amine N-H bonds. Here we introduce a protecting-group-free approach for the α-functionalization of cyclic secondary amines. An operationally simple one-pot procedure generates products via a process that involves intermolecular hydride transfer to generate an imine intermediate that is subsequently captured by a nucleophile, such as an alkyl or aryl lithium compound. Reactions are regioselective and stereospecific and enable the rapid preparation of bioactive amines, as exemplified by the facile synthesis of anabasine and (-)-solenopsin A.
Topics: Alkaloids; Amines; Anabasine; Chemistry Techniques, Synthetic; Molecular Structure; Stereoisomerism
PubMed: 29359746
DOI: 10.1038/nchem.2871 -
Journal of Chromatography. B,... Jan 2021Tobacco use, of which cigarette smoking is the most common, is a global health concern and is directly linked to over 7 million premature deaths annually. Measurement of...
Tobacco use, of which cigarette smoking is the most common, is a global health concern and is directly linked to over 7 million premature deaths annually. Measurement of the levels of tobacco-related biomarkers in biological matrices reflects human exposure to the chemicals in tobacco products. Nicotine, nicotine metabolites, anatabine, and anabasine are specific to tobacco and nicotine containing products. However, as nicotine and its metabolites are ubiquitous in the environment, background contamination during sample preparation can occur, making the quantification of target analytes challenging. The main purpose of the present study was to examine quality control measures needed in the determination of urinary nicotine, nicotine metabolites, anatabine, and anabasine. Urine samples (n = 75) and NIST standard reference materials SRM 3671 and SRM 3672 were analysed. A one-step extraction procedure using cold acetone was used in this study, which involved no additional clean up. The blank matrices investigated included synthetic urine prepared with HPLC-grade water, synthetic urine prepared with Milli-Q water, and bovine urine. By adopting strategies for minimizing the background levels, very low detection limits for all the target analytes ranging from 0.025 ng/mL for 3-hydroxycotinine to 0.634 ng/mL for nicotine, were achieved. Recoveries ranged between 67% and 118% with RSD values below 20%. Intra-day and inter-day precisions were in the range of 1.1-11.7% and 4.8-25.2%, respectively. The levels of all target analytes were higher in daily smokers than in non-smokers, with the largest difference observed for 3-hydroxycotinine. No difference was observed in the levels of target analytes between individuals who were former smokers, who never smoked or who were exposed to environmental tobacco smoke (ETS), except for total nicotine equivalents (TNE), which was significantly higher in non-smokers exposed to environmental tobacco smoke compared with study participants who never smoked. The results obtained from SRM 3671 and SRM 3672 could inform a potential certification of additional biomarkers of exposure to tobacco products in those standard reference materials.
Topics: Adolescent; Adult; Animals; Biomarkers; Cattle; Chromatography, High Pressure Liquid; Environmental Exposure; Female; Humans; Limit of Detection; Linear Models; Male; Middle Aged; Nicotine; Reproducibility of Results; Tandem Mass Spectrometry; Tobacco Products; Tobacco Smoke Pollution; Young Adult
PubMed: 33360416
DOI: 10.1016/j.jchromb.2020.122490 -
Clinical and Experimental Rheumatology 2021At present, the pathogenesis of Sjögren's syndrome (SS) remains unclear. This research aimed to identify differential metabolites that contribute to SS diagnosis and...
OBJECTIVES
At present, the pathogenesis of Sjögren's syndrome (SS) remains unclear. This research aimed to identify differential metabolites that contribute to SS diagnosis and discover the disturbed metabolic pathways.
METHODS
Recent advances in mass spectrometry have allowed the identification of hundreds of unique metabolic signatures and the exploration of altered metabolite profiles in disease. In this study, 505 candidates including healthy controls (HCs) and SS patients were recruited and the serum samples were collected. A non-targeted gas chromatography-mass spectrometry (GC-MS) serum metabolomics method was used to explore the changes in serum metabolites.
RESULTS
We found SS patients and HCs can be distinguished by 21 significant metabolites. The levels of alanine, tryptophan, glycolic acid, pelargonic acid, cis-1-2-dihydro-1-2-naphthalenediol, diglycerol, capric acid, turanose, behenic acid, dehydroabietic acid, stearic acid, linoleic acid, heptadecanoic acid, valine, and lactic acid were increased in serum samples from SS patients, whereas levels of catechol, anabasine, 3-6-anhydro-D-galactose, beta-gentiobiose, 2-ketoisocaproic acid and ethanolamine were decreased. The significantly changed pathways included the following: Linoleic acid metabolism; unsaturated fatty acid biosynthesis; aminoacyl-tRNA biosynthesis; valine, leucine, and isoleucine biosynthesis; glycerolipid metabolism; selenocompound metabolism; galactose metabolism; alanine, aspartate and glutamate metabolism; glyoxylate and dicarboxylate metabolism; glycerophospholipid metabolism; and valine, leucine and isoleucine degradation.
CONCLUSIONS
These findings enhance the informative capacity of biochemical analyses through the identification of serum biomarkers and the analysis of metabolic pathways and contribute to an improved understanding of the pathogenesis of SS.
Topics: Biomarkers; Humans; Metabolomics; Sjogren's Syndrome
PubMed: 34251320
DOI: 10.55563/clinexprheumatol/ylte6v -
Drug Testing and Analysis Jul 2016Wastewater analysis, the chemical analysis of municipal sewage, is fast becoming the technique of choice to monitor changes in community consumption of a range of...
Wastewater analysis, the chemical analysis of municipal sewage, is fast becoming the technique of choice to monitor changes in community consumption of a range of compounds over time. Currently wastewater analyses which estimate tobacco consumption focus on the major alkaloid nicotine and its urinary metabolite, cotinine. As nicotine is also present in replacement therapies such as nicotine gum and patches, this analysis is not specific and hence does not truly reflect the harmful consumption of tobacco. Two alkaloids - anabasine and anatabine - which are specific to dried tobacco, were assessed as biomarkers for tobacco consumption in wastewater, together with nicotine and cotinine. Consequently, solid phase extraction (SPE) and liquid chromatography-mass spectrometry (LC-MS) methods for the detection of anabasine, anatabine, nicotine, and cotinine in municipal wastewater were validated. All compounds were detected in wastewater extracts and found to have satisfactory recovery, accuracy, precision, and stability in wastewater. Daily flow volume and catchment population of the wastewater facility were used to estimate normalized consumption figures of mg/day/1000 people for composite samples collected over one week, in an application of the method. Anabasine and anatabine were found to be suitable wastewater biomarkers of tobacco and can be used to assess tobacco consumption of communities via wastewater analysis. Application of this methodology can be used to collect temporal consumption data which could be used to determine the efficacy of tobacco reduction strategies. Copyright © 2015 John Wiley & Sons, Ltd.
Topics: Alkaloids; Anabasine; Chromatography, Liquid; Cotinine; Humans; Limit of Detection; Mass Spectrometry; Nicotine; Pyridines; Solid Phase Extraction; Tobacco Use; Wastewater; Water Pollutants, Chemical
PubMed: 26198173
DOI: 10.1002/dta.1842 -
Heliyon May 2019N'-Nitrosonornicotine (NNN), a carcinogenic tobacco-specific N'-nitrosamine (TSNA), is on the FDA list of harmful and potentially harmful constituents (HPHCs)....
N'-Nitrosonornicotine (NNN), a carcinogenic tobacco-specific N'-nitrosamine (TSNA), is on the FDA list of harmful and potentially harmful constituents (HPHCs). Nornicotine, a product of the demethylation of nicotine, is the immediate alkaloid precursor for NNN formation. Nicotine, nornicotine and NNN are optically active. The accumulation of the isomers of nicotine, nornicotine, and NNN impacts their biological activity. In this paper, we report the determination of tobacco alkaloid enantiomers (including nicotine, nornicotine, anabasine, and anatabine) in samples of different tobacco lines using a reversed phase ultra-performance liquid chromatography-tandem mass spectrometer (UPLC/MS/MS) method. Current method demonstates excellent detection capability for all alkaloid enantiomers, with correlation coefficients (r) > 0.996 within their linear dynamic ranges. The limit of detection (LOD) and limit of quantitation (LOQ) of all analytes are less than 10 ng/mL and 30 ng/mL, respectively. In addition, their recovery and coefficient of variation (CV%) are within 100-115% and 0.2-3.7%, respectively. The method validated in this paper is simple, fast, and sensitive for the quantification of alkaloid enantiomers in tobacco leaf and has been applied to investigations of tobacco alkaloid enantiomer ratios in different tobacco lines and tobacco products.
PubMed: 31193304
DOI: 10.1016/j.heliyon.2019.e01719 -
Natural Product Research Jun 2017The decline of pollinating species is correlated to the extensive use of neonicotinoids against pest insects for crop protection. In this study, the concentrations of...
The decline of pollinating species is correlated to the extensive use of neonicotinoids against pest insects for crop protection. In this study, the concentrations of neonicotinoid insecticides were determined in honeybees, honeycomb and honey samples, collected in Spring 2015 (blooming period) from different areas in Sicily (IT), to carry out an evaluation of bees products' safety and an overview of neonicotinoid contamination in beekeeping. The results obtained showed only the presence of clothianidin in bee samples and these concentrations don't represent a risk for bees' vitality and safety. The absence of residue in all honey samples, instead, showed the quality of bee products.
Topics: Anabasine; Animals; Beekeeping; Bees; Environmental Monitoring; Guanidines; Honey; Insecticides; Neonicotinoids; Pesticides; Pollination; Sicily; Thiazoles
PubMed: 27736155
DOI: 10.1080/14786419.2016.1236101 -
Journal of Analytical Toxicology Sep 2014Laboratory detection of nicotine exposure is important for establishing eligibility for organ transplant and elective surgery. Nicotine testing is also used to verify...
Laboratory detection of nicotine exposure is important for establishing eligibility for organ transplant and elective surgery. Nicotine testing is also used to verify compliance with nicotine replacement therapies (NRT), smoking cessation programs and for life insurance purposes. Nicotine metabolites, such as cotinine and trans-3'-hydroxycotinine, are used as biomarkers of nicotine exposure. For some clinical applications, it is important to distinguish between active use of tobacco products versus NRT. Anabasine is a tobacco alkaloid that has been used as a biomarker of active tobacco use. However, the use of anabasine as an insecticide, and its presence in consumables other than nicotine products, suggests that anabasine may not be specific to tobacco use/exposure. Here, we determine the reference interval for anabasine in the urine of nonsmokers and compare it to the range of anabasine concentrations observed in the presence or absence of nicotine metabolites.
Topics: Anabasine; Biomarkers; Calibration; Chromatography, Liquid; Female; Healthy Volunteers; Humans; Male; Nicotine; Patient Compliance; Reference Values; Reproducibility of Results; Smoking; Smoking Cessation; Substance Abuse Detection; Surveys and Questionnaires; Tandem Mass Spectrometry; Tobacco Use Cessation Devices
PubMed: 24939383
DOI: 10.1093/jat/bku059 -
Proceedings. Biological Sciences Mar 2015The synthesis of secondary metabolites is a hallmark of plant defence against herbivores. These compounds may be detrimental to consumers, but can also protect...
The synthesis of secondary metabolites is a hallmark of plant defence against herbivores. These compounds may be detrimental to consumers, but can also protect herbivores against parasites. Floral nectar commonly contains secondary metabolites, but little is known about the impacts of nectar chemistry on pollinators, including bees. We hypothesized that nectar secondary metabolites could reduce bee parasite infection. We inoculated individual bumblebees with Crithidia bombi, an intestinal parasite, and tested effects of eight naturally occurring nectar chemicals on parasite population growth. Secondary metabolites strongly reduced parasite load, with significant effects of alkaloids, terpenoids and iridoid glycosides ranging from 61 to 81%. Using microcolonies, we also investigated costs and benefits of consuming anabasine, the compound with the strongest effect on parasites, in infected and uninfected bees. Anabasine increased time to egg laying, and Crithidia reduced bee survival. However, anabasine consumption did not mitigate the negative effects of Crithidia, and Crithidia infection did not alter anabasine consumption. Our novel results highlight that although secondary metabolites may not rescue survival in infected bees, they may play a vital role in mediating Crithidia transmission within and between colonies by reducing Crithidia infection intensities.
Topics: Alkaloids; Anabasine; Animals; Bees; Crithidia; Disease Resistance; Glycosides; Host-Parasite Interactions; Plant Nectar; Secondary Metabolism; Terpenes
PubMed: 25694627
DOI: 10.1098/rspb.2014.2471 -
Proceedings. Biological Sciences Jul 2014There is evidence that in Europe and North America many species of pollinators are in decline, both in abundance and distribution. Although there is a long list of... (Review)
Review
There is evidence that in Europe and North America many species of pollinators are in decline, both in abundance and distribution. Although there is a long list of potential causes of this decline, there is concern that neonicotinoid insecticides, in particular through their use as seed treatments are, at least in part, responsible. This paper describes a project that set out to summarize the natural science evidence base relevant to neonicotinoid insecticides and insect pollinators in as policy-neutral terms as possible. A series of evidence statements are listed and categorized according to the nature of the underlying information. The evidence summary forms the appendix to this paper and an annotated bibliography is provided in the electronic supplementary material.
Topics: Anabasine; Animals; Bees; Insecticides; Pollination
PubMed: 24850927
DOI: 10.1098/rspb.2014.0558 -
Journal of Ethnopharmacology Dec 2023Crossbow-medicine needle therapy (microneedle roller combined with crossbow-medicine) is one of the external treatment methods of Miao Medicine in China. It is a way of...
Effect of microneedle roller on promoting transdermal absorption of crossbow-medicine liquid via transdermal administration of Traditional Chinese Medicine and the safety of crossbow-medicine needle therapy: An experimental study.
ETHNOPHARMACOLOGY RELEVANCE
Crossbow-medicine needle therapy (microneedle roller combined with crossbow-medicine) is one of the external treatment methods of Miao Medicine in China. It is a way of combining acupuncture with Chinese herbal medicine, which is widely used in clinical treatment of pain.
AIM OF THE STUDY
To observe the transdermal absorption promoting effect of microneedle roller via transdermal administration, and to discuss the transdermal absorption characteristics and the safety of crossbow-medicine needle therapy.
METHODS
Based on the determination of the content of the main components of crossbow-medicine prescription in our previous research, the present experiment was conducted in-vitro and in-vivo experiments and the skin of rats was used as the penetration barrier. For in-vitro experiment, the modified Franz diffusion cell method was used to determine the transdermal absorption rate and 24h cumulative transdermal absorption amount of the active ingredients of crossbow-medicine liquid. For in-vivo experiment, tissue homogenization was applied to compare the skin retention amount and plasma concentration of crossbow-medicine liquid absorbed at different time points via the aforementioned two modes of administration. Furthermore, the effect of crossbow-medicine needle on the morphological structure of rat skin stratum corneum was detected by hematoxylin-eosin (HE) staining. The safety of crossbow-medicine needle therapy was evaluated according to the scoring criteria of the skin irritation test.
RESULTS
1. In-vitro experiment: In the microneedle-roller group and crossbow-medicine liquid application group, the effect of transdermal delivery was identified in all the four ingredients of anabasine, chlorogenic acid, mesaconitine and hypaconitine. The 24h cumulative transdermal absorption amount and transdermal absorption rate of each ingredient in microneedle-roller group were significantly higher than those in crossbow-medicine liquid application group (all P < 0.05). 2. In-vivo experiment: Both microneedle-roller and crossbow-medicine liquid application could promote the transdermal absorption of the active ingredients of the drug in the skin and retain in the skin structure. After 8h of administration, the total retention amount of anabasine, chlorogenic acid, mesaconitine and hypaconitine in the skin of rats in the former group was significantly higher than that in the latter group (all P < 0.05). 3. HE staining: In the blank group, the stratum corneum showed an evenly zonal distribution on the active epidermis, and had a close connection with the epidermis, without exfoliation or cell dissociation of the stratum corneum. The crossbow-medicine liquid group had a relatively complete stratum corneum, with a small proportion of exfoliation or cell dissociation, loose arrangement and loose connection with the epidermis. In the microneedle-roller group, the skin had pore channels, and the stratum corneum was loose and exfoliated, which showed zonal distribution in a free state and a high degree of separation. The crossbow-medicine needle group had loose the stratum corneum, broken and exfoliated, which was separated from the active epidermis and showed zonal distribution in a free state. 4.
SAFETY
No obvious erythema, edema and skin protuberance were observed in the skin of rats treated with microneedle roller, crossbow-medicine liquid and crossbow-medicine needle. Additionally, the skin irritative response score was 0.
CONCLUSION
Microneedle roller can promote the transdermal absorption of crossbow-medicine liquid, and crossbow-medicine needle therapy has good safety.
Topics: Rats; Animals; Skin Absorption; Administration, Cutaneous; Medicine, Chinese Traditional; Anabasine; Chlorogenic Acid; Skin; Needles
PubMed: 37295573
DOI: 10.1016/j.jep.2023.116751