Attila Sipos
University of Debrecen, Department of Pharmaceutical Chemistry, Faculty Member
... Page 2. Sipos Attila Doktori (PhD) értekezés ii Köszönetnyilvánítás Köszönöm Prof. Antus Sándor akadémikus, tanszékvezető egyetemi tanárnak, hogy Ph.D. értekezésem elkészítését a Szerves Kémiai Tanszéken lehetővé tette. Köszönöm... more
... Page 2. Sipos Attila Doktori (PhD) értekezés ii Köszönetnyilvánítás Köszönöm Prof. Antus Sándor akadémikus, tanszékvezető egyetemi tanárnak, hogy Ph.D. értekezésem elkészítését a Szerves Kémiai Tanszéken lehetővé tette. Köszönöm témavezetőmnek Dr. Berényi Sándor ...
Energy-dependent collision-induced dissociation (CID) of the dimers [2 M + Cat](+) of the noscapine and hydrastine stereoisomers was studied where Cat stands for Li(+) , Na(+) , K(+) and Cs(+) ions. These dimers were generated... more
Energy-dependent collision-induced dissociation (CID) of the dimers [2 M + Cat](+) of the noscapine and hydrastine stereoisomers was studied where Cat stands for Li(+) , Na(+) , K(+) and Cs(+) ions. These dimers were generated 'in situ' from the electrosprayed solution. The survival yield (SY) method was used for distinguishing the noscapine and hydrastine dimers. Significant differences were found between the characteristic collision energies (CE50 , i.e. the collision energy necessary to obtain 50% fragmentation) of the homo- (R,R; S,S) and heterochiral (R,S; S,R) stereoisomers. To distinguish the enantiomer pairs L-, D-tyrosine ([M + Tyr + Cat](+) ) and L-, D-lysine ([M + Lys + Cat](+) ) were used as chiral selectors. Furthermore, these heterodimers [M + amino acid + Cat](+) were also applied to determine the stereoisomeric composition. It was found that the characteristic collision energy (CE50 ) of the noscapine and hydrastine homodimers ([2 M + Cat](+) ) was inversely proportional to the ionic radius of the cations. Furthermore, the structures of the dimers [2 M + Cat](+) were studied by high level quantum chemical calculations. Copyright © 2015 John Wiley & Sons, Ltd.
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The fragmentation properties of singly and doubly lithiated polytetrahydrofuran (PTHF) were studied using energy-dependent collision-induced dissociation. The product ion spectrum of [PTHF + Li](+) showed the formation of three different... more
The fragmentation properties of singly and doubly lithiated polytetrahydrofuran (PTHF) were studied using energy-dependent collision-induced dissociation. The product ion spectrum of [PTHF + Li](+) showed the formation of three different series corresponding to product ions with hydroxyl, aldehyde and vinyl end-groups. Interestingly, besides these series, two additional, non-lithiated product ions C(4)H(9)O(+) and C(4)H(7)(+) were identified in the MS/MS spectra. The MS/MS of the doubly lithiated PTHF ([PTHF + 2Li](2+)) with a number of repeat units ranging from 8 to 27 showed the formation of product ions similar to those of the singly lithiated series, however, doubly lithiated product ions and product ions formed by the loss of one Li(+)-ion from the precursor ion also appeared with significant abundances. Analysis of the breakdown curves for the singly and doubly charged PTHF indicated that the series A ions are formed most probably together with the series B ions, while members of the series C ions appeared at significantly higher collision energies. The fragmentation properties of [PTHF + Li](+) and [PTHF + 2Li](2+) were also interpreted using the survival yield method. It was found that the collision energy/voltage necessary to obtain 50% fragmentation (CV(50)) was dependent linearly on the number of the repeat units, i.e., on the size, or the number of degrees of freedom (DOF).
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Research Interests:
Goldenseal (Hydrastis canadensis) is one of the best- selling herbal drugs on the largest market of the World. There is a traditional American folk use of this remedy which is now extended for treatment of... more
Goldenseal (Hydrastis canadensis) is one of the best-
selling herbal drugs on the largest market of the World.
There is a traditional American folk use of this remedy which is now extended for treatment of skin disorders, digestive problems, liver disease, diarrhea and eye
irritations among other health issues. Current descriptions of the medicinal herb contains references regarding the action of inhibition or killing many microorganisms, including fungi, protozoa and bacteria; however, on the basis of experimental results, the most common uses
including the prevention and treatment of flu are questionable. Here we collected the most recent research results reflecting on the anti-infective properties of
Hydrastis canadensis and its two major alkaloids (berberine and (+)-β-hydrastine) suspected to be responsible for such
activities. Additionally the possibilities of drug interactions and the questions of potential synergism of Goldenseal and the major components were discussed. The contribution of berberine to the development of multidrug pump inhibitors and the new directions of this
remarkable area are summerized as well.
selling herbal drugs on the largest market of the World.
There is a traditional American folk use of this remedy which is now extended for treatment of skin disorders, digestive problems, liver disease, diarrhea and eye
irritations among other health issues. Current descriptions of the medicinal herb contains references regarding the action of inhibition or killing many microorganisms, including fungi, protozoa and bacteria; however, on the basis of experimental results, the most common uses
including the prevention and treatment of flu are questionable. Here we collected the most recent research results reflecting on the anti-infective properties of
Hydrastis canadensis and its two major alkaloids (berberine and (+)-β-hydrastine) suspected to be responsible for such
activities. Additionally the possibilities of drug interactions and the questions of potential synergism of Goldenseal and the major components were discussed. The contribution of berberine to the development of multidrug pump inhibitors and the new directions of this
remarkable area are summerized as well.
Research Interests:
Research Interests:
Research Interests:
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full... more
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
The autooxidation phenomenon of apomorphine and the products of this procedure were analytically and pharmacologically studied, however we found that there have been some unclarified details of this filed. Therefore the synthesis and... more
The autooxidation phenomenon of apomorphine and the products of this procedure were analytically and pharmacologically studied, however we found that there have been some unclarified details of this filed. Therefore the synthesis and structure of the autooxidation products of three clinically and pharmacologically relevant aporphinoids (apomoprine, N-propyl-norapomorphine and 2-hydroxy-N-propyl-norapomorphine) were thoroughly investigated. The autooxidation of apomorphine achieved at physiological pH resulted two products; one of them is the known tetracyclic, tertiary amino ortho quinone and the hitherto unknown, fluorescent, derivatized phenanthrene-3,4-quinone. Under the same conditions N-propyl congeners resulted only the expected 1,2-dione products. The analytical structure elucidation involved the full 1H and 13C NMR assignment, UV and IR characterizations of the four isolated ortho quinone-type products exploiting the possibilities of DFT calculations for geometry optimization, NMR and IR simulations. The phenanthrene-3,4-quinone compound can be relevant in further pharmacological studies of aporphine-related oxidation products due to its potential toxicity and investigated fluorescent character.► The autooxidation phenomenon of apomorphine. ► Synthesis and structure elucidation of the autooxidation products of three aporphinoids. ► Characterization of a hitherto unknown, fluorescent, derivatized phenanthrene-3,4-quinone. ► Structure elucidation with 1H and 13C NMR, UV and IR spectra using DFT calculations.
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ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full... more
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Abstract The synthesis of 4H-thiochromene derivatives of apomorphines, a novel class of isoquinoline alkaloid-related compounds, has been achieved by different O-dealkylation methods applied on previously published heteroring-fused... more
Abstract The synthesis of 4H-thiochromene derivatives of apomorphines, a novel class of isoquinoline alkaloid-related compounds, has been achieved by different O-dealkylation methods applied on previously published heteroring-fused aporphinoids. Detailed DFT study has been presented regarding the mechanism of the L-selectride-mediated multiple O-dealkylation of a seven-ring aporphine analogue. Dopamine-binding tests confirmed the essential function of 11-hydroxy moiety of the aporphine skeleton and revealed a remarkable D1 over D2 specificity for the derivative having the 4H-thiochromene ring system attached to positions 2 and 3 of the aporphine backbone. Graphical Abstract
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The one-pot N-demethylation and acid-catalyzed rearrangement of morphinan-N-oxides offers a new, shorter and more efficient route to neuropharmacologically important N-substituted aporphines. An improved procedure is described for the... more
The one-pot N-demethylation and acid-catalyzed rearrangement of morphinan-N-oxides offers a new, shorter and more efficient route to neuropharmacologically important N-substituted aporphines. An improved procedure is described for the preparation of the starting alkaloid N-oxides using Na2WO4 as catalyst. The transetherification during the rearrangement of codeinone into 2-O-alkyl-norapocodeines is documented.
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ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full... more
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Abstract Three independent strategies have been established for the synthesis of morphinans with oxazole moieties derived from the aminophenol function of 2-aminomorphine. All the procedures possess the ability to furnish diversely... more
Abstract Three independent strategies have been established for the synthesis of morphinans with oxazole moieties derived from the aminophenol function of 2-aminomorphine. All the procedures possess the ability to furnish diversely substituted 2′-oxazole moieties which are considered significant in view of the presented density functional studies on the spatial and electrostatic properties of the proximal functions of the 3-hydroxyl of the morphinan backbone. These data are considered important for neuropharmacological development of potential kappa antagonist morphinans. The second strategy was extended to the direct vinylation of oxazoles to form more complex benzoxazole-type morphinans. Graphical abstract
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A set of novel 6-substituted orvinols was synthesized and pharmacologically characterized in order to explore the effect of the polarity and steric effects of these new moieties on the opioid activity. It was revealed that longer... more
A set of novel 6-substituted orvinols was synthesized and pharmacologically characterized in order to explore the effect of the polarity and steric effects of these new moieties on the opioid activity. It was revealed that longer 6-O-alkyl chains led to increased agonistic activities, while the lack of C6-etheral oxygen gave rise to an antagonistic profile at the opioid receptors in the mouse ileum.Nanomolar affinity to opioid receptors and antagonistic profile at the opioid receptors in the mouse ileum.
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Six monoprotected acetals and -thioacetals of glutaradehyde and its symmetrical dimethyl derivatives were synthesized. Microwave-assisted heating proved to be a substantially more selective method for monoprotection than conventional... more
Six monoprotected acetals and -thioacetals of glutaradehyde and its symmetrical dimethyl derivatives were synthesized. Microwave-assisted heating proved to be a substantially more selective method for monoprotection than conventional heating. All reactions were efficient and only traces of diprotected material were formed.
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Two synthesis routes have been elaborated for the preparation of novel N-substituted-2-alkyl- and 2-arylnorapomorphines. The first one utilizes the traditional methodology of N-substitution of morphinans before acid-catalyzed... more
Two synthesis routes have been elaborated for the preparation of novel N-substituted-2-alkyl- and 2-arylnorapomorphines. The first one utilizes the traditional methodology of N-substitution of morphinans before acid-catalyzed rearrangements into aporphinoids, while our new approach involves the N-substitution directly on the aporphine backbone. The aimed compounds were obtained in similar overall yields in different synthesis routes and were investigated with respect to their binding affinities and activities to dopamine D2 and D1 receptors. These studies revealed remarkable affinity and selectivity of some compounds for D2 over D1 receptor subtypes. Partial or full agonist properties were confirmed for all tested compounds.
Research Interests: Organic Chemistry, Suzuki Miyaura cross-coupling, Cell line, Vitamin D receptor, Animals, and 11 moredopamine receptor D4, Rats, Oxidation, Bioorganic and medicinal Chemistry, Biological activity, Structure activity Relationship, Protein Binding, Chemical Synthesis, Apomorphine, Binding affinity, and fibroblasts
A novel strategy has been developed for the synthesis of ring A fused thiazolomorphinans and ring D fused thiazoloaporphines offering the possibility of formation of regioisomeric products. The conventional thermal thiazole-forming... more
A novel strategy has been developed for the synthesis of ring A fused thiazolomorphinans and ring D fused thiazoloaporphines offering the possibility of formation of regioisomeric products. The conventional thermal thiazole-forming reaction was replaced with microwave initiation and a detailed discussion has been presented on the proposed mechanism of the ring closure.
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A simple synthesis of ring-constrained endoethenomorphinans possessing 2'-substituted thiazole ring 4-6 has been achieved by... more
A simple synthesis of ring-constrained endoethenomorphinans possessing 2'-substituted thiazole ring 4-6 has been achieved by regio- and stereoselective Diels-Alder reaction of thiazolomorphinandienes 1-3 and methyl vinyl ketone in high yield (72, 64 and 87%, respectively). The structure of cycloaddition products was determined by high resolution mass spectrometry (HRMS), IR, 1D and 2D NMR techniques. Double-pulsed field gradient spin-echo-nOe and HMBC were found to be particularly powerful and indispensable tools in the exact structural elucidation of the presented new class of spatially constrained thevinones.
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Research Interests:
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ABSTRACT The formation of 1,4-thiazine and benzo-1,4-thiazine rings was performed at the 6,7-positions of the morphinan backbone in order to synthesize systems annulated with a new six-membered ring providing potential pharmacological... more
ABSTRACT The formation of 1,4-thiazine and benzo-1,4-thiazine rings was performed at the 6,7-positions of the morphinan backbone in order to synthesize systems annulated with a new six-membered ring providing potential pharmacological activity and the opportunity of easy functionalization. An unexpected oxidation of cyclic sulfur was observed in both cases affording either sulfones or open-ringed bis-morphinan-type by-product. These phenomena are in conformity with the observations and mechanistic explanations made by several research groups in the past in connection with the photosensitized oxidation of cyclic sulfides.Graphical abstractThe formation of 1,4-thiazine and benzo-1,4-thiazine rings was performed at the 6,7-positions of the morphinan backbone in order to synthesize systems annulated with a new six-membered ring providing potential pharmacological activity and the opportunity of easy functionalization. An unexpected oxidation of cyclic sulfur was observed in both cases affording either sulfones or open-ringed bis-morphinan-type by-product.
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Abstract The synthesis and acid-catalyzed rearrangement of novel thiazolomorphinandienes have been presented. An isomerization was observed simultaneously with the backbone transformation. An extensive study was performed to determine the... more
Abstract The synthesis and acid-catalyzed rearrangement of novel thiazolomorphinandienes have been presented. An isomerization was observed simultaneously with the backbone transformation. An extensive study was performed to determine the major effects of the isomerization of 2′-alkyl- and aryl-substituted thiazoloapocodeines into 3′-alkyl- and arylisothiazoloapocodeines. The obtained results provided another practical example of the reversible benzisothiazole–benzothiazole-type isomerization emphasizing the determining role of the thermal effects in the occurrence of these isomerization products. The obtained experimental results and the proposed mechanism were in agreement with the calculated DFT data. Graphical abstract
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... Backbone. Attila Sipos*, Sándor Berényi*. Department ... morphinan. Garrido and co-workers studied the oxidative behavior of apomorphine in aqueous media giving raise to some norapomorphines as a result of anodic oxidation. [10 ...
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Research Interests:
... The authors are grateful for the substantial discussion with Sándor Antus and for the financial support from the National Science Foundation (Grant OTKA Reg. Nos. ... [Taylor & Francis Online], [Web of Science ®]; 4.... more
... The authors are grateful for the substantial discussion with Sándor Antus and for the financial support from the National Science Foundation (Grant OTKA Reg. Nos. ... [Taylor & Francis Online], [Web of Science ®]; 4. Csutorás, C., Berényi, S., Czakó, B. and Makleit, S. 1997. ...
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We have presented the synthesis of novel thiazolo- and isothiazolo-apomorphines 12–17 resulting–in part–from an unexpected isomerization step occurred during the acid-catalyzed rearrangement of precursor thiazolo-morphinandienes 3–5.... more
We have presented the synthesis of novel thiazolo- and isothiazolo-apomorphines 12–17 resulting–in part–from an unexpected isomerization step occurred during the acid-catalyzed rearrangement of precursor thiazolo-morphinandienes 3–5. These 2,3-disubstituted apomorphines represent a new group of A-ring substituted aporphines. The receptor binding studies revealed that with the exception of two derivatives all the tested compounds have limited affinity for dopamine-receptor subtypes. Functional calcium assay for the most active isothiazolo-apomorphine showed higher affinities for D1 and D2L subtypes. The docking of these ligands has been modelled to human D2 and D3 receptors. On the basis of the predicted models, we identified an important cation-p interaction for the binding of isothiazolo-apomorphine 16.
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We have synthesized novel 2-O-substituted apomorphines with both different lengths of lipophilic alkyl chains and alkyl chains carrying free hydroxyl groups. Two bis-apomorphines formed as side products of the reactions with diols were... more
We have synthesized novel 2-O-substituted apomorphines with both different lengths of lipophilic alkyl chains and alkyl chains carrying free hydroxyl groups. Two bis-apomorphines formed as side products of the reactions with diols were isolated and characterized as well. The neuropharmacological profile of all these new compounds were investigated with respect to their binding affinities and activities to dopamine D2 and D1 receptors. The obtained data pointed to the fact that, in the examination of dopaminergic activities of 2-substituted apomorphines, the lipophilicity of the substituent is more important than its spatial parameters.We have synthesized novel 2-O-substituted apomorphines with both different lengths of lipophilic alkyl chains and alkyl chains carrying free hydroxyl groups. Two bis-apomorphines formed as side products of the reactions with diols were isolated and characterized as well. The neuropharmacological profile of all these new compounds was investigated with respect to their binding affinities and activities to dopamine D2 and D1 receptors. The obtained data pointed to the fact that, in the examination of dopaminergic activities of 2-substituted apomorphines, the lipophilicity of the substituent is more important than its spatial parameters.