Demissidine

Synthesis of Demissidine and Solanidine.[Pubmed:27232858]

Org Lett. 2016 Jun 17;18(12):3038-40.

Demissidine and solanidine, two steroidal alkaloids, are synthesized in eight steps from tigogenin acetate and diosgenin acetate, respectively, which involve the replacement of three C-O bonds with C-N bonds. Key transformations include a cascade ring-switching process of furostan-26-acid, an epimerization of C25, an intramolecular Schmidt reaction, and an imine reduction/intramolecular aminolysis process.

Optimisation and validation of ultra-high performance liquid chromatographic-tandem mass spectrometry method for qualitative and quantitative analysis of potato steroidal alkaloids.[Pubmed:26102635]

J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Aug 1;997:110-5.

An ultra-high performance liquid chromatographic-tandem mass spectrometry (UHPLC-MS/MS) method for quantification of potato steroidal alkaloids, namely alpha-solanine, alpha-chaconine, solanidine and Demissidine was developed and validated. Three different column chemistries, i.e. ethylene bridged hybrid (BEH) C18, hydrophilic lipophilic interaction and amide columns, were assessed. The BEH C18 column showed best separation and sensitivity for the alkaloids. Validation data (inter-day and intra-day combined) for accuracy and recovery ranged from 94.3 to 107.7% and 97.0 to 103.5%, respectively. The accuracy data were within the acceptable range of 15% as outlined in the United States Food and Drug Administration (USFDA) guidelines. The recovery data were consistent and reproducible with a coefficient of variation (CV) ranging from 6.2 to 9.7%. In addition, precision of the method also met the criteria of the USFDA with CV values lower than 15% even at lower limit of quantification (LLOQ), while the permissible variation is considered acceptable below 20%. The limit of detection and LLOQ of the four alkaloids were in the range of 0.001-0.004mug/mL whereas the linearities of the standard curves were between 0.980 and 0.995.

Recovery of steroidal alkaloids from potato peels using pressurized liquid extraction.[Pubmed:25985357]

Molecules. 2015 May 13;20(5):8560-73.

A higher yield of glycoalkaloids was recovered from potato peels using pressurized liquid extraction (1.92 mg/g dried potato peels) compared to conventional solid-liquid extraction (0.981 mg/g dried potato peels). Response surface methodology deduced the optimal temperature and extracting solvent (methanol) for the pressurized liquid extraction (PLE) of glycoalkaloids as 80 degrees C in 89% methanol. Using these two optimum PLE conditions, levels of individual steroidal alkaloids obtained were of 597, 873, 374 and 75 microg/g dried potato peel for alpha-solanine, alpha-chaconine, solanidine and Demissidine respectively. Corresponding values for solid liquid extraction were 59%, 46%, 40% and 52% lower for alpha-solanine, alpha-chaconine, solanidine and Demissidine respectively.

Ultrasonic extraction of steroidal alkaloids from potato peel waste.[Pubmed:24582305]

Ultrason Sonochem. 2014 Jul;21(4):1470-6.

Potato processors produce large volumes of waste in the form of potato peel which is either discarded or sold at a low price. Potato peel waste is a potential source of steroidal alkaloids which are biologically active secondary metabolites which could serve as precursors to agents with apoptotic, chemopreventive and anti-inflammatory properties. The present study investigated the relative efficacy of ultrasound assisted extraction (UAE) and solid liquid extraction (SLE) both using methanol, to extract steroidal alkaloids from potato peel waste and identified optimal conditions for UAE of alpha-solanine, alpha-chaconine, solanidine and Demissidine. Using response surface methodology optimal UAE conditions were identified as an amplitude of 61 mum and an extraction time of 17 min which resulted the recovery of 1102 mug steroidal alkaloids/g dried potato peel (DPP). In contrast, SLE yielded 710.51 glycoalkaloid mug/g DPP. Recoveries of individual glycoalkoids using UAE yielded 273, 542.7, 231 and 55.3 mug/g DPP for alpha-solanine, alpha-chaconine, solanidine and Demissidine respectively. Whereas for SLE yields were 180.3, 337.6, 160.2 and 32.4 mug/g DPP for alpha-solanine, alpha-chaconine, solanidine and Demissidine respectively. The predicted values from the developed second order quadratic polynomial equation were in close agreement with the experimental values with low average mean deviation (E<5%) values. Predicted models were highly significant (p<0.05) for all parameters studied. This study indicates that UAE has strong potential as an extraction method for steroidal alkaloids from potato peel waste.

Synthesis of demissidine by a ring fragmentation 1,3-dipolar cycloaddition approach.[Pubmed:23586838]

Org Lett. 2013 May 3;15(9):2100-3.

A synthesis of the steroidal alkaloid Demissidine from epiandrosterone is reported. A ring fragmentation reaction that efficiently ruptured the D-ring of a diazo ester derivative of epiandrosterone to provide an aldehyde tethered ynoate product was key to this sequence. Incorporation of the indolizidine framework was achieved by an azomethine ylide 1,3-dipolar cycloaddition.

Elucidation of the mass fragmentation pathways of potato glycoalkaloids and aglycons using Orbitrap mass spectrometry.[Pubmed:20641001]

J Mass Spectrom. 2010 Sep;45(9):1019-25.

The mass fragmentation of potato glycoalkaloids, alpha-solanine and alpha-chaconine, and the aglycons, Demissidine and solasodine were studied using the Orbitrap Fourier transform (FT) mass spectrometer. Using the linear ion trap (LIT) mass spectrometry, multistage collisional-induced dissociation (CID) experiments (MS(n)) on the [M + H](+) precursor ions were performed to aid the elucidation of the mass fragmentation pathways. In addition, higher energy collisional-induced dissociation (HCD) mass spectra were generated for these toxins at a high resolution setting [100,000 FWHM (full width at half maximum)] using the Orbitrap. This hybrid mass spectrometry instrumentation was exploited to produce MS(3) spectra by selecting MS(2) product ions, generated using LIT MS, and fragmentation using HCD. The accurate mass data in the MS(3) spectra aided the confirmation of proposed product ion formulae. The precursor and product ions from glycoalkaloids lost up to four sugars from different regions during MS(n) experiments. Mass fragmentation of the six-ring aglycons were similar, generating major product ions that resulted from cleavages at the B-rings and E-rings.

Distribution of glycoalkaloids in potato tubers of 59 accessions of two wild and five cultivated Solanum species.[Pubmed:19053181]

J Agric Food Chem. 2008 Dec 24;56(24):11920-8.

Steroidal glycoalkaloids are naturally occurring, secondary plant metabolites that are found in foods, including potatoes and tomatoes. Their content in plants is controlled by both genetic and environmental factors. Glycoalkaloid profiles can be passed to progenies during breeding and hybridization of wild and cultivated potatoes designed to develop improved potatoes. The most common potato, Solanum tuberosum, contains primarily the glycoalkaloids, alpha-solanine and alpha-chaconine. However, wild-type potatoes being used for breeding new varieties contain other, less common glycoalkaloids. Because glycoalkaloid composition is a major criterion for the release of new potato cultivars, we used HPLC, TLC, GC, and GC/MS to determine their nature and content in several Solanum species widely used in potato breeding and hybridization programs. Solanum tuberosum, as well as S. andigena and S. stenotomum, contained alpha-solanine and alpha-chaconine. S. canasense was found to contain only dehydrocommersonine. S. acaule contained alpha-tomatine and demissine. S. juzepczukii and S. curtilobum contained demissine and two previously unidentified glycoalkaloids. We characterized them as Demissidine-glucose/rhamnose (1/1 ratio) and Demissidine-galactose/glucose/rhamnose (1/1/1 ratio), tentatively named dihydro-beta(1)-chaconine and dihydrosolanine, respectively. We found extensive variability in the glycoalkaloid profiles in the tested potato varieties. The possible significance of these findings for plant breeding and food safety is discussed.

Alkaloids induce programmed cell death in bloodstream forms of trypanosomes (Trypanosoma b. brucei).[Pubmed:18833031]

Molecules. 2008 Oct 3;13(10):2462-73.

The potential induction of a programmed cell death (PCD) in Trypanosoma b. brucei by 55 alkaloids of the quinoline, quinolizidine, isoquinoline, indole, terpene, tropane, steroid, and piperidine type was studied by measuring DNA fragmentation and changes in mitochondrial membrane potential. For comparison, the induction of apoptosis by the same alkaloids in human leukemia cells (Jurkat APO-S) was tested. Several alkaloids of the isoquinoline, quinoline, indole and steroidal type (berberine, chelerythrine, emetine, sanguinarine, quinine, ajmalicine, ergotamine, harmine, vinblastine, vincristine, colchicine, chaconine, Demissidine and veratridine) induced programmed cell death, whereas quinolizidine, tropane, terpene and piperidine alkaloids were mostly inactive. Effective PCD induction (EC(50) below 10 microM) was caused in T. brucei by chelerythrine, emetine, sanguinarine, and chaconine. The active alkaloids can be characterized by their general property to inhibit protein biosynthesis, to intercalate DNA, to disturb membrane fluidity or to inhibit microtubule formation.

Compartmentalization of oxidative stress and antioxidant defense in the larval gut of Spodoptera littoralis.[Pubmed:16921519]

Arch Insect Biochem Physiol. 2006 Sep;63(1):1-10.

Allelochemicals play important roles in the plant defense against herbivorous insects. They act as feeding deterrents, interfere with digestion and nutrient absorption, and cause production of potentially dangerous oxidative radicals. This study demonstrates that the distributions of oxidative radicals and of the antioxidant enzymes that eliminate them are compartmentalized in the digestive tract of Spodoptera littoralis larvae. Feeding on diets supplemented with the tannic acid (TA), alpha-solanine, and Demissidine, respectively, did not affect the rate of food passage through the digestive tract of larvae but 1.25, 2.5, and 5% TA evoked a strong oxidative response. The amount of the superoxide anion in the foregut tissue and content increased up to 70-fold and the titer of total peroxides in the foregut content about 3-fold. This oxidative stress was associated with enhanced carbonyl content in the foregut tissue proteins, indicative of certain tissue deterioration. Extensive foregut damage was probably prevented by elevated activity of the glutathione S-transferase peroxidase. A complex antioxidant response was elicited in the midgut. The activities of superoxide dismutase and catalase increased significantly in the midgut tissue and content, and the activity of ascorbate peroxidase rose in the midgut tissue. The enzymes apparently eliminated oxidative radicals passing to midgut from the foregut with the food bolus and thereby prevented carbonylation of the midgut proteins. We postulate that the generation of oxidative radicals in the foregut and the induction of antioxidant defense in the midgut are controlled processes and that their compartmentalization is an important functional feature of the digestive tract. The glycoalkaloid alpha-solanine and the aglycone Demissidine applied at 0.05 and 0.1% concentrations had no effect on any of the examined parameters.

Glycoalkaloid aglycone accumulations associated with infection by Clavibacter michiganensis ssp. sepedonicus in potato species Solanum acaule and Solanum tuberosum and their interspecific somatic hybrids.[Pubmed:15365763]

Plant Cell Rep. 2005 Mar;23(10-11):683-91.

Solanum acaule Bitt., a wild potato species, is closely related to cultivated potato (Solanum. tuberosum L.). Incorporation of desirable traits from allotetraploid [2n=4x=48, 2 endosperm balance number (EBN)] S. acaule (acl) into autotetraploid (2n=4x=48, 4EBN) S. tuberosum (tbr) is difficult due to incongruity boundaries. In this study, three hybrid combinations, each with a specific genome constitution, were produced through protoplast fusion: (1) hexaploid 2x acl (+) 4x tbr, (2) tetraploid 2x acl (+) 2x tbr, and (3) hexaploid 4x acl (+) 2x tbr hybrids. In terms of glycoalkaloid aglycones, the hybrids produced Demissidine, tomatidine and solanidine, similarly to the S. acaule parental species, but S. tuberosum synthesised only solanidine. Inoculations with Clavibacter michiganensis ssp. sepedonicus (Cms), which is the causal agent of bacterial ring rot in potato, yielded significantly lower total glycoalkaloid aglycone accumulation both in S. acaule plants and in interspecific hybrids in comparison with the corresponding mock-inoculated plants. However, in S. tuberosum the aglycone levels were either higher or unchanged as a result of infection by Cms. To incorporate the desirable traits of the interspecific somatic hybrids into 4EBN S. tuberosum, sexual backcrosses were carried out. The hexaploid 4x acl (+) 2x tbr hybrids with the hypothetical 4EBN showed the greatest capacity to undergo backcrosses with S. tuberosum.

Glycoalkaloids and metabolites inhibit the growth of human colon (HT29) and liver (HepG2) cancer cells.[Pubmed:15137822]

J Agric Food Chem. 2004 May 19;52(10):2832-9.

As part of an effort to improve plant-derived foods such as potatoes, eggplants, and tomatoes, the antiproliferative activities against human colon (HT29) and liver (HepG2) cancer cells of a series of structurally related individual compounds were examined using a microculture tetrazolium (MTT) assay. The objective was to assess the roles of the carbohydrate side chain and aglycon part of Solanum glycosides in influencing inhibitory activities of these compounds. Evaluations were carried out with four concentrations each (0.1, 1, 10, and 100 microg/mL) of the the potato trisaccharide glycoalkaloids alpha-chaconine and alpha-solanine; the disaccharides beta(1)-chaconine, beta(2)-chaconine, and beta(2)-solanine; the monosaccharide gamma-chaconine and their common aglycon solanidine; the tetrasaccharide potato glycoalkaloid dehydrocommersonine; the potato aglycon Demissidine; the tetrasaccharide tomato glycoalkaloid alpha-tomatine, the trisaccharide beta(1)-tomatine, the disaccharide gamma-tomatine, the monosaccharide delta-tomatine, and their common aglycon tomatidine; the eggplant glycoalkaloids solamargine and solasonine and their common aglycon solasodine; and the nonsteroidal alkaloid jervine. All compounds were active in the assay, with the glycoalkaloids being the most active and the hydrolysis products less so. The effectiveness against the liver cells was greater than against the colon cells. Potencies of alpha-tomatine and alpha-chaconine at a concentration of 1 microg/mL against the liver carcinoma cells were higher than those observed with the anticancer drugs doxorubicin and camptothecin. Because alpha-chaconine, alpha-solanine, and alpha-tomatine also inhibited normal human liver HeLa (Chang) cells, safety considerations should guide the use of these compounds as preventative or therapeutic treatments against carcinomas.

Interaction of folk medicinal plant extracts with human alpha2-adrenoceptor subtypes.[Pubmed:12064736]

Z Naturforsch C J Biosci. 2002 Mar-Apr;57(3-4):332-8.

Forty-two extracts of folk medicinal plant organs from Pakistan were tested in competition binding assays for their interaction with the specific ligand recognition sites on the human alpha2-adrenoceptor subtypes alpha2A, alpha2B and alpha2C Strong binding of the extracts (40 mg/ml) from Acacia nilotica (L.) Delile leaves (88-98% displacement of radiolabel) and Peganum harmala seeds (89-96% displacement) on three subtypes prompted us to extract these plant materials with 40% and 80% methanol, ethanol, and acetone. The extraction results indicated an absence of alpha2-adrenoceptor binding activity in the stalk of A. nilotica and A. tortils, whereas the leaves of both plants contained activity. The extracts of A. nilotica leaves showed a slight, but consistent, preference for the alpha2C-adrenoceptor, whereas the leaves of A. tortils were slightly more active on the alpha2B subtype. The extract of P. harmala stalks was less active than that of its seeds. The binding activities of A. nilotica leaves and P. harmala seeds were mainly concentrated in the water and 30% methanol fractions and further sub-fractions. In a functional activity assay, the active fractions inhibited epinephrine-stimulated 35S-GTPyS binding, thus indicating a predominantly antagonistic nature of the compounds with alpha2-adrenoceptor affinity in these fractions. Among the known major alkaloids of P. harmala (Demissidine, harmaline, harmine, 6-methoxyharmalan, and norharmane), only 6-methoxyharmalan showed moderate affinity (dissociation constant (Ki) of 530 +/- 40 nm for alpha2A subtype). This study is a first systematic attempt towards the discovery of potential drug candidates from these plant materials for treating alpha2-adrenoceptor related diseases.

Non-aqueous capillary electrophoresis with diode array and electrospray mass spectrometric detection for the analysis of selected steroidal alkaloids in plant extracts.[Pubmed:11486878]

J Chromatogr A. 2001 Jul 13;922(1-2):321-8.

Nonaqueous capillary electrophoresis coupled to UV detection is described for the separation and determination of steroidal alkaloids. After optimization of electrophoretic parameters, including the electrolyte nature and the organic solvent composition, a reliable separation of solasodine and solanidine was achieved in a methanol-acetonitrile (20:80, v/v) mixture containing 25 mM ammonium acetate and 1 M acetic acid. For quantitative purposes, a fused-silica capillary with a bubble cell was used and detection was performed at low wavelength (195 nm). Method performances, including migration time and peak area reproducibility, linearity, sensitivity and accuracy, were also evaluated. The method was applied to determine solasodine in Solanum elaeagnifolium berries and Solanum sodomaeum leaves and seeds. To further improve sensitivity in the analysis of solasodine-related compounds, solanidine, Demissidine and tomatidine, the developed method was interfaced with electrospray ionization mass spectrometry. In the case of solasodine, the detection limit was estimated at 3 microg/ml for NACE-UV and at 0.05 microg/ml for NACE-MS, in the selected ion-monitoring mode.

Inhibition of Trypanosoma cruzi growth in vitro by Solanum alkaloids: a comparison with ketoconazole.[Pubmed:9491766]

Planta Med. 1998 Feb;64(1):31-6.

The glycoalkaloids alpha-chaconine, alpha-solamargine, alpha-solanine, solasonine, sycophantine, and tomatine, as well as the aglycones Demissidine, solanidine, solanocapsine, solasodine, tomatidine, and veratrine were tested as growth inhibitors of Trypanosoma cruzi, strain EP, in LIT medium. Their activity was compared with the antifungal ketoconazole. Glycoalkaloids containing alpha-chacotriose showed trypanolytic activity against the epimastigote form and trypanocidal activity against the bloodstream and metacyclic trypomastigote form of Trypanosoma cruzi in culture medium in micromolar concentrations. Ketoconazole showed a lower activity, at the same concentrations of alpha-chaconine and alpha-solamargine. The observations indicate that the initial target of the compound is at the membrane level with a concomitant change in the parasite morphology. Moreover, internal compartments of the parasites were observed to be affected by the drugs, revealing the dissolution of some organelles as mitocondrias and glycosomes.