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“Synthesis and α-Adrenoreceptor Blocking Properties of Phenoxybenzamine-Related (2-Chloroethyl)-(2,3-dihydrobenzo-[1,4] dioxin-2-ylmethyl)-(2-phenoxyethyl) Amines”.
No full textIsolation of Soyasaponins I e VI from soybeans by semipreparatives HPLC and characterization by mass spectrometry.
No full textINTRODUCTION
Saponins are triterpenoid or steroid glycosides naturally occurring in plants. Soyasaponins from soy and other legumes are the primary dietary sources of food saponins. Soyasaponins have been demonstrated to lower cholesterol level by inhibiting its absorption, be anti-carcinogenic and antihepatotoxic, and show anti-replicative properties against HIV. Lentils, one of the richest and cheapest sources of vegetable proteins, mainly contain soyasaponin I and soyasaponin VI. Because of the difficulties to obtain authentic, high purity soyasaponin standards, especially in the case of thermolabile soyasaponin VI, we started a project aiming at isolating pure soyasaponins I and VI from soybeans, to be used for quantitative analysis of soyasaponin content in various Italian cultivars of lentils.
MATERIALS AND METHODS
Extraction and purification of saponins were performed as follows: dried and finely ground soybeans were extracted with ethanol, then the alcoholic solution was filtered and concentrated. The crude extract was purified on a C18 flash-chromatographic column using acetonitrile-water as eluting mixture (gradient); the collected fractions, containing both soyasaponins, were injected in a semipreparative HPLC system equipped with a C18 column using a mixture of methanol/water, containing acetic acid, as mobile phase. Each saponin was detected at its specific wavelength: 206 nm for soyasaponin I, and 292 nm for soyasaponin VI. After HPLC analysis, the pure soyasaponins I and VI were collected and their structures identified using the HPLC-ESI-IT (Ion Trap), performing MSn experiments and studying their typical fragmentations.
RESULTS AND DISCUSSION
With the above described method, we have been able to obtain pure soyasaponins with high purity (soyasaponin I: 80%; soyasaponin VI: 91%), which was assessed using HPLC-DAD at 206 and 292 nm
Ink photoinitiators determination in cartboard packagings and contained food by GC/MS and HPLC/MS/MS.
No full textINTRODUCTION
The alert for food contamination by photoinitiators, a class of molecules used in UV-cured inks for printing the surface of polycoupled carton used as container for liquid food, arose in Europe in November 2005, when the Italian authorities withdraw from the market thirty million liters of infants milk, because of contamination with the photoinitiator 2-isopropylthioxanthone (ITX).
Regarding effects of ITX on human health, there are contradictory opinions; in fact, no fully convincing data on ITX genotoxicity have been published to date. Very recently, a paper reported that ITX can affect the mobility/rigidity status of biological membranes by strong interactions with the cellular lipid bilayer.
After that alert, factories producing cartonboard stated that no more ITX was used in packagings.
MATERIALS AND METHODS
In the present research, we developed and applied to market food samples a multiresidue method for the simultaneous detection and quantification of five of the most commonly used photoinitiators and co-initiators, namely ITX, 2-ethylhexyl-4-dimethylaminobenzoate (EHDAB), Benzophenone, 1-hydroxycyclohexyl-1-phenyl ketone (IRGACURE 184), and ethyl-4-dimethylaminobenzoate (EDAB). Those contaminants were analyzed using gas chromatography–mass spectrometry (GC/MS) and liquid chromatography–mass spectrometry (LC/MS) techniques, both on the cartonboard packagings and contained liquid food; the method was applied to milk, fruit juices, and wine, previously purified by solid-phase extraction (SPE).
RESULTS AND DISCUSSION
Benzophenone was found in all forty analyzed food samples in a concentration range of 5–217 μg l−1. EHDAB was found in eleven beverages in a concentration range of 0.13–0.8 μg l−1, while ITX was found in three samples in a range 0.2–0.24 μg l−1. The proposed methods showed to be robust and reliable for the determination of the five analyzed contaminants in food
Resolution of the potent alpha1-adrenoreceptor antagonist 2-[[[2-(2,6-dimethoxyphenoxy)ethyl]amino]methyl]-1,4-benzoxathian (benoxathian)
No full textThe enantiomers of 2-[[[2-(2,6-dimethoxyphenoxy)ethyl]amino]methyl]-1,4-benzoxathian hydrochloride (1: benoxathian) were prepared from the chiral 1,4-benzoxathian-2-carboxylic acids [(+)- and (−)-3] which in turn were obtained through the resolution of the racemic acid with R- and S-alpha-methylbenzylamine. Their blocking activities and relative selectivities on alpha1- and alpha2-adrenoreceptors were evaluated on isolated rat vas deferens. For alpha1-adrenoreceptors the enantiomer (−)-1 was 10 times more potent than the enantiomer (+)-1, whereas no significant difference between the blocking activity of the enantiomers was observed for alpha2-adrenoreceptors. Furthermore, the enantiomer (−)-1 showed high activity and selectivity toward the alpha1-adrenoreceptor (pA2 = 9.36; selectivity ratio = 1230) which may have relevance in the characterization of alpha-adrenoreceptor subtypes
Set up of a quick screening method for determination of heavy metals in food, including wine.
No full textINTRODUCTION
A number of heavy metals are essential for development of plants and animals at trace concentration, whereas they are toxic at higher levels. Toxicity risk is made higher by their ability to give bioaccumulation and biomagnification. Human being, at the top of food chain, is particularly exposed to this risk
From the above, it is clear that heavy metal levels are regulated by national and international laws. For wine, at least in the European Community, highest allowable levels are of 200 ppb for Lead (Pb) and 5 ppm for Zinc (Zn).
Routine analysis of food needs robust, quick, and cheap methods for quantification. Up to now, the official method for heavy metal determination in food relays on Atomic Absorption Spectrometry (AAS), which requires time and money consuming pre-treatment of samples for mineralization of them.
MATERIALS AND METHODS
In the present work, we developed, validated, and applied to market samples a new and innovative metod for the analysis of Zn and Pb in wine, based on Energy Dispersive X-ray analysis (EDX) method. Pre-instrumental work-up is very simple, consisting essentially in the concentration of wine under analysis. Residue is analyzed “as is” in the EDX instrument.
RESULTS AND DISCUSSION
The above described methodology has been validated analyzing 20 samples of wine, bought in local markets, both with the innovative EDX method and with the more conventional AAS method. Results show that the new method presents high reliability, and could be the method of choice for a quick screening of an high number of samples. Furthermore, Zn and Pb levels in analyzed samples ranged from 0,130 to 0,450 ppm, and from 19 to 78 ppb, respectively, with no sample showing concentration of either metal above the allowed ones
Polymethylene tetraamines as muscarinc receptor probes
No full textThe possibility that polymethylene tetraamines act as divalent ligands has been explored. Structure-activity relationship studies among polymethylene tetraamines have shown that four nitrogens are necessary for high affinity binding to M2 receptors while being less important for M3 muscarinic receptors. Replacement of one terminal methoxybenzyl group of the potent and selective muscarinic antagonist methoctramine by different moieties led to weaker antagonists suggesting that the two terminal nitrogens of methoctramine interact with two similar receptor sites. Data are presented which suggest that methoctramine might interact with four acidic residues of the receptor: two residues are buried in the third transmembrane segment whereas the others are located extracellularly on the loop 4-5 which may represent the allosteric site where several antagonists such as gallamine bind. An hypothetical model describing the interaction of methoctramine with the M2 receptor is proposed. It may provide a useful working hypothesis for the design of new selective muscarinic ligands
Structure-activity relationships among benextramine-related tetraamine disulfides. Chain length effect on alpha-adrenoreceptor blocking activity1
No full textSeveral N'-substituted N,N"-(dithiodi-2,1-ethanediyl)bis(1,w-alkanediamines) were prepared and evaluated for their blocking activity on alpha-adrenoreceptors in the isolated rat vas deferens and human blood platelets. The results were compared with those obtained for benextramine (N,N"-(dithiodi-2,1-ethanediyl)bis[N'-[(2-methoxyphenyl)-methyl]-1,6-hexanediamine], 10). Bendotramine (N,N"-(dithiodi-2,1-ethanediyl)bis[N'-[(2-methoxyphenyl)-methyl]-1,12-dodecanediamine], 16) proved to be as active as 10 on alpha1-adrenoreceptors, showing that optimum activity is associated with two carbon chain lengths separating inner from outer nitrogens of tetraamine disulfides. On the other hand, 16 had no activity up to 20 microM at alpha2-adrenoreceptors. The optimum activity at this receptor subtype was associated with a six to eight carbon chain (10-12). Furthermore, 10 proved to be more selective toward alpha-adrenoreceptors whereas 16 was a selective alpha1-antagonist. The tetraamine disulfides were shown also to be potent inhibitors of human platelet aggregation induced by ADP or epinephrine. The potency increased with the carbon chain length. However, the results on platelets did not parallel those found in the rat vas deferens, indicating that differences exist between the alpha-adrenoreceptor subtypes investigated. In conclusion, 10 may be a useful tool in characterizing alpha2-adrenoreceptors whereas 16 might help in investigating alpha1-adrenoreceptors
Structure-activity relationships among benextramine-related tetraamine disulfides at peripheral alpha-adrenoreceptors
No full textSeveral N,N'’-(dithiodi-2,1-ethanediyl)bis[N’-(arylmethyl)-1,6-hexanediamines] were prepared and evaluated for their blocking activity on postsynaptic alpha1-adrenoreceptors in the isolated rat vas deferens. The results were compared with those obtained for benextramine (1). N,N’'-(Dithiodi-2,1-ethanediyl)bis[N’-(pyrrol-2-ylmethyl)-1,6-hexanediamine] (pyrextramine, 29) was the most potent among the tetraamine disulfides investigated. Thus, it was selected for further pharmacological evaluation to assess its receptor specificity. At a concentration of 10 microM it did not affect
the responses elicited by 5-hydroxytryptamine and histamine in guinea pig ileum and by isoproterenol in guinea pig atria and tracheal chain. Furthermore, it was more specific than benextramine (1) toward the muscarinic receptor, being significantly less potent in inhibiting the carbachol-induced response in rat jejunum. These results show that pyrextramine (29) is an irreversible a-blocking agent that is more potent and specific than benextramine (1). In conclusion, 29 may be a useful tool in the elucidation and characterization of the peripheral alpha1-adrenoreceptor
Structure-activity relationships among methoctramine-related polymethylene tetraamines. Chain-length and substituent effects on M2-muscarinic receptor blocking activity.
No full textSeveral polymethylene tetraamines related to methoctramine (1) were prepared and evaluated for their blocking activity on M-2 muscarinic receptors in guinea pig atria and ileum. It turned out that antimuscarinic potency depends on the following parameters: (a) nature of the substituent on both inner and outer nitrogens and (b) carbon chain length separating the inner nitrogens as well as the inner and outer nitrogens. Optimum activity at cardiac M-2 muscarinic receptors was associated with the chain lengths present in 1, that is, eight methylenes between the inner nitrogens and six methylenes between the inner and outer nitrogens. With regard to the substitueats, replacement of the benzylic moiety of 1 by a 2-fury1 or a 5-methyl-2-fury1 nucleus resulted in enhanced potency toward cardiac M-2 muscarinic receptors. In fact, furtramine (18) and mefurtramine (19) proved to be more potent and more selective than 1. Moreover, N-methylation of the four nitrogens of 1 gave different effects: methylation of the outer nitrogens, giving 22, caused a significant decrease in activity whereas methylation of the inner nitrogens, yielding 23, resulted in an increase in activity in both atria and ileum
Chiral analogues of (+)-cyclazosin as potent α1B-adrenoceptor selective antagonist
No full text(+)-Cyclazosin [(+)-1] is one of most selective antagonists of the α1B-adrenoceptor subtype (selectivity ratios, α1B/α1A = 13, α1B/α1D = 38–39). To improve the selectivity, we synthesized and pharmacologically studied the blocking activity against α1-adrenoceptors of several homochiral analogues of (+)-cyclazosin featuring different substituents on the carbonyl or amine groups, namely (−)-2, (+)-3, (−)-4–(−)-8, (+)-9. Moreover, we studied the activity of some their opposite enantiomers, namely (−)-1, (−)-3, (+)-6, and (−)-9, to evaluate the influence of stereochemistry on selectivity. The benzyloxycarbonyl and methyl (4aS,8aR) analogues (+)-3 and (−)-6 improved in a significant way the α1B selectivity of the progenitor compound: 4 and 14 time vs. the α1D subtype and 35 and 77 times vs. the α1A subtype, respectively. The study confirmed the importance of the hydrophobic cis-octahydroquinoxaline moiety of these molecules for the establishment of interactions with the α1-adrenoceptors as well that of their (4aS,8aR) stereochemistry to grant selectivity for the α1B subtype. Hypotheses on the mode of interaction of these compounds were advanced on the basis of molecular modeling studies performed on compound (+)-3
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