The glucosinolates (GSLs) is a well-defined group of plant metabolites characterized by having an S-β-d-glucopyrano unit anomerically connected to an O-sulfated (Z)-thiohydroximate function. After ...enzymatic hydrolysis, the sulfated aglucone can undergo rearrangement to an isothiocyanate, or form a nitrile or other products. The number of GSLs known from plants, satisfactorily characterized by modern spectroscopic methods (NMR and MS) by mid-2018, is 88. In addition, a group of partially characterized structures with highly variable evidence counts for approximately a further 49. This means that the total number of characterized GSLs from plants is somewhere between 88 and 137. The diversity of GSLs in plants is critically reviewed here, resulting in significant discrepancies with previous reviews. In general, the well-characterized GSLs show resemblance to C-skeletons of the amino acids Ala, Val, Leu, Trp, Ile, Phe/Tyr and Met, or to homologs of Ile, Phe/Tyr or Met. Insufficiently characterized, still hypothetic GSLs include straight-chain alkyl GSLs and chain-elongated GSLs derived from Leu. Additional reports (since 2011) of insufficiently characterized GSLs are reviewed. Usually the crucial missing information is correctly interpreted NMR, which is the most effective tool for GSL identification. Hence, modern use of NMR for GSL identification is also reviewed and exemplified. Apart from isolation, GSLs may be obtained by organic synthesis, allowing isotopically labeled GSLs and any kind of side chain. Enzymatic turnover of GSLs in plants depends on a considerable number of enzymes and other protein factors and furthermore depends on GSL structure. Identification of GSLs must be presented transparently and live up to standard requirements in natural product chemistry. Unfortunately, many recent reports fail in these respects, including reports based on chromatography hyphenated to MS. In particular, the possibility of isomers and isobaric structures is frequently ignored. Recent reports are re-evaluated and interpreted as evidence of the existence of “isoGSLs”, i.e. non-GSL isomers of GSLs in plants. For GSL analysis, also with MS-detection, we stress the importance of using authentic standards.
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•List of glucosinolates characterized satisfactorily using NMR and MS data, in total 88.•Selected glucosinolate structures deduced indirectly, in total 47.•Review of glucosinolate nomenclature, chemistry, organic synthesis and plant biochemistry.•Review of glucosinolate identification and guidelines for scientific reporting.
The organic sulfur-containing compounds glucosinolates (GSLs) and the novel gasotransmitter H2S are known to have cardioprotective effects. This study investigated the antioxidant effects and ...H2S-releasing potential of three GSLs ((3E)-4-(methylsulfanyl)but-3-enyl GSL or glucoraphasatin, 4-hydroxybenzyl GSL or glucosinalbin, and (RS)-6-(methylsulfinyl)hexyl GSL or glucohesperin) in rat cardiac cells. It was found that all three GSLs had no effect on cardiac cell viability but were able to protect against H2O2-induced oxidative stress and cell death. NaHS, a H2S donor, also protected the cells from H2O2-stimulated oxidative stress and cell death. The GSLs alone or mixed with cysteine, N-acetylcysteine, glutathione, H2O2, iron and pyridoxal-5′-phosphate, or mouse liver lysates did not induce H2S release. The addition of GSLs also did not alter endogenous H2S levels in cardiac cells. H2O2 significantly induced cysteine oxidation in the cystathionine gamma-lyase (CSE) protein and inhibited the H2S production rate. In conclusion, this study found that the three tested GSLs protect cardiomyocytes from oxidative stress and cell death but independently of H2S signaling.
The cultivated Lepidium latifolium L. was investigated to decipher its glucosinolate profile, antimicrobial, and cytotoxic activities. HPLC/ESI‐MS analyses of the intact glucosinolates and GC/MS ...analysis of their hydrolysis products showed the presence of sinigrin (1), glucocochlearin (2), glucotropaeolin (3), and 4‐methoxyglucobrassicin (4). Hydrodistillate, extract, and allyl isothiocyanate, the main volatile resulting from sinigrin degradation, showed antimicrobial activity against all eleven tested pathogenic and food spoilage bacteria and fungi, with highest effect observed against Candida albicans with MIC50 8 and 16 μg/mL. Hydrodistillate and extract showed the best cytotoxic activity on bladder cancer UM‐UC‐3 cell line during an incubation time of 24 h (IC50 192.9 and 133.8 μg/mL, respectively), while the best effect on glioblastoma LN229 cell line was observed after 48 h (IC50 110.8 and 30.9 μg/mL, respectively). Pure allyl isothiocyanate displayed a similar trend in cytotoxic effect on both cell lines (IC50 23.3 and 36.5 μg/mL after 24 h and 48 h, respectively).
A general pathway was devised to synthesize ω-methylsulfanylalkyl glucosinolates, which represent an important class of structurally homogeneous plant secondary metabolites. The required ...thiofunctionalized hydroximoyl chlorides were obtained from the corresponding α,ω-nitroalkyl methylsulfide precursors, involving as the key-step, a nitronate chlorination strategy. A coupling reaction with 1-thio-
-d-glucopyranose, followed by
-sulfation of the intermediate thiohydroximate and final deprotection of the sugar moiety afforded the target compounds.
Glucosinolates (GSLs) from Lepidium graminifolium L. were analyzed qualitatively and quantitatively by their desulfo-counterparts using UHPLC-DAD-MS/MS technique and by their volatile breakdown ...products-isothiocyanates (ITCs) using GC-MS analysis. Thirteen GSLs were identified with arylaliphatic as the major ones in the following order: 3-hydroxybenzyl GSL (glucolepigramin, 7), benzyl GSL (glucotropaeolin, 9), 3,4,5-trimethoxybenzyl GSL (11), 3-methoxybenzyl GSL (glucolimnanthin, 12), 4-hydroxy-3,5-dimethoxybenzyl GSL (3,5-dimethoxysinalbin, 8), 4-hydroxybenzyl GSL (glucosinalbin, 6), 3,4-dimethoxybenzyl GSL (10) and 2-phenylethyl GSL (gluconasturtiin, 13). GSL breakdown products obtained by hydrodistillation (HD) and CH2Cl2 extraction after hydrolysis by myrosinase for 24 h (EXT) as well as benzyl ITC were tested for their cytotoxic activity using MTT assay. Generally, EXT showed noticeable antiproliferative activity against human bladder cancer cell line UM-UC-3 and human glioblastoma cell line LN229, and can be considered as moderately active, while IC50 of benzyl ITC was 12.3 μg/mL, which can be considered as highly active.
This review gives a survey of the chemistry, occurrence and biological properties of 4-methylsulfanyl-3-butenyl glucosinolate, known as glucoraphasatin.
Glucoraphasatin is an atypical glucosinolate ...mainly found in
Raphanus sativus roots and sprouts. This review focuses on the chemistry, the occurrence, and the biological properties of glucoraphasatin.
Flaxseed oil is widely recognized for its exceptional nutritional value, high concentration of fiber-based lignans and large amounts of ω-fatty acids. It is one of a generic group of functional foods ...that is often taken by cancer patients as a potential treatment. We have examined the anti-cancer effects of flaxseed oil by studying its direct effects on cancer cell growth in vitro. Treatment of a variety of cancer cell lines with flaxseed oil decreased their growth in a dose-dependent manner while non-malignant cell lines showed small increases in cell growth. Cells treated with a mixture of fatty acids, including α-linolenic acid, docosahexaenoic acid, and eicosapentaenoic acid and lignans including enterodiol and enterolactone was also able to decrease the growth of cancer cells. Treatment of B16-BL6 murine melanoma and MCF-7 breast cancer cells with flaxseed oil induced apoptosis as determined by changes in cell morphology, annexin V staining, DNA fragmentation and/or caspase activation. In addition, treatment with flaxseed oil also disrupted mitochondrial function in B16-BL6 and MCF-7 cells. These results indicate that flaxseed oil can specifically inhibit cancer cell growth and induce apoptosis in some cancer cells and suggests it has further potential in anti-cancer therapy.
Hydrogen sulfide (H2S) was originally considered toxic at elevated levels; however just in the past decade H2S has been proposed to be an important gasotransmitter with various physiological and ...pathophysiological roles in the body. H2S can be generated endogenously from L-cysteine by multiple enzymes, including cystathionine gamma-lyase, cystathionine beta-synthase, and 3-mercaptopyruvate sulfurtransferase in combination with cysteine aminotransferase. Prostate cancer is a major health concern and no effective treatment for prostate cancers is available. H2S has been shown to inhibit cell survival of androgen-independent, androgen-dependent, and antiandrogen-resistant prostate cancer cells through different mechanisms. Various H2S-releasing compounds, including sulfide salts, diallyl disulfide, diallyl trisulfide, sulforaphane, and other polysulfides, also have been shown to inhibit prostate cancer growth and metastasis. The expression of H2S-producing enzyme was reduced in both human prostate cancer tissues and prostate cancer cells. Androgen receptor (AR) signaling is indispensable for the development of castration resistant prostate cancer, and H2S was shown to inhibit AR transactivation and contributes to antiandrogen-resistant status. In this review, we summarized the current knowledge of H2S signaling in prostate cancer and described the molecular alterations, which may bring this gasotransmitter into the clinic in the near future for developing novel pharmacological and therapeutic interventions for prostate cancer.
The addictive nature of nicotine is likely the most significant reason for the continued prevalence of tobacco smoking despite the widespread reports of its negative health effects. Nicotine vaccines ...are an alternative to the currently available smoking cessation treatments, which have limited efficacy. However, the nicotine hapten is non-immunogenic, and successful vaccine formulations to treat nicotine addiction require both effective adjuvants and delivery systems. The immunomodulatory properties of short, non-natural peptide sequences not found in human systems and their ability to improve vaccine efficacy continue to be reported. The aim of this study was to determine if small "non-natural peptides," as part of a conjugate nicotine vaccine, could improve immune responses. Four peptides were synthesized via solid phase methodology, purified, and characterized.
plasma stability studies using RP-HPLC confirmed that the peptides were not subject to proteolytic degradation. The peptides were formulated into conjugate nicotine vaccine candidates along with a bacterial derived adjuvant vaccine delivery system and chitosan as a stabilizing compound. Formulations were tested
in a dendritic cell line to determine the combination that would elicit the greatest 1L-1β response using ELISAs. Three of the peptides were able to enhance the cytokine response above that induced by the adjuvant delivery system alone.
vaccination studies in BALB/c mice demonstrated that the best immune response, as measured by nicotine-specific antibody levels, was elicited from the conjugate vaccine structure, which included the peptide, as well as the other components. Isotype analyses highlighted that the peptide was able to shift immune response toward being more humorally dominant. Overall, the results have implications for the use of non-natural peptides as adjuvants not only for the development of a nicotine vaccine but also for use with other addictive substances and conventional vaccination targets as well.
Indolyl-3-acetaldoxime dehydratase was identified as the protein SS1G_01653 from
Sclerotinia sclerotiorum with the molecular mass of 44
kDa.
The purification and characterization of ...indolyl-3-acetaldoxime dehydratase produced by the plant fungal pathogen
Sclerotinia sclerotiorum is described. The substrate specificity indicates that it is an indolyl-3-acetaldoxime dehydratase (IAD, EC 4.99.1.6), which catalyzes transformation of indolyl-3-acetaldoxime to indolyl-3-acetonitrile. The enzyme showed Michaelis–Menten kinetics and had an apparent molecular mass of 44
kDa. The amino acid sequence of IAD, determined using LC–ESI-MS/MS, identified it as the protein SS1G_01653 from
S. sclerotiorum. IADSs was highly homologous (84% amino acid identity) to the hypothetical protein BC1G_14775 from
Botryotinia fuckeliana B05.10. In addition, similarity to the phenylacetaldoxime dehydratases from
Gibberella zeae (33% amino acid identity) and
Bacillus sp. (20% amino acid identity) was noted. The specific activity of IADSs increased about 17-fold upon addition of Na
2S
2O
4 under anaerobic conditions, but in the absence of Na
2S
2O
4 no significant change was observed, whether aerobic or anaerobic conditions were used. As with other aldoxime dehydratases isolated from microbes, the role of IADSs in fungal plant pathogens is not clear, but given its substrate specificity, it appears unlikely that IADSs is a general xenobiotic detoxifying enzyme.
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