Добірка наукової літератури з теми "Derivative of o-aminobenzoic acids"

An investigation has been carried out into the Schlack-Kumpf reaction, i.e., the reaction of amino acids with a mixture of acetic anhydride, acetic acid and sodium thiocyanate (occasionally ammonium thiocyanate was used). Particular emphasis was placed on the reactions with amino acids containing sensitive or functional side chains, i.e., serine, threonine , arginine , proline , lysine, histidine , cysteine , and aspartic and glutamic acids. The reaction of serine, and of certain of its O- and N-substituted derivatives, takes an unusual course to give an acetylated thiohydantoin derivative of cysteine. Correspondingly, threonine gives an acetylated thiohydantoin derivative of β- methylcysteine. Similar reactions occurred with the 3-phenylthiohydantoin derivatives of serine and of threonine to give acetylated thiohydantoin derivatives of cysteine and of β-methylcysteine respectively.

Steroid O-(ω-hydroxyalkyl)oximes with varying alkyl chain length were prepared from the corresponding carboxylic acids using the reduction of mixed anhydrides with sodium borohydride. An unexpected reaction course was observed with O-(2-carboxyethyl)oximes of 3-oxo-4-ene steroids, where a 4,5-dihydroisoxazol-3(2H)-one derivative was formed as a side product.

Together with ten well known compounds, the quinic acid derivative chlorogenic acid, the nucleoside adenosine, two amino acids, tryptophan and phenylalanine, the anthraquinone derivatives, aloemodin, aloemodin acetate and chyrosphanol 1-O-gentiobioside, the flavon C-glycosides, isovitexin, isoorientin and isoorientin 4’-O-β -glucopyranoside, as well as two new acylated isoorientin derivatives, 6”-O-(malonyl)-isoorientin and 6”-O-[(S)-3-hydroxy-3-methylglutaroyl]-isoorientin, were isolated from the water soluble part of the methanolic extract of the fresh leaves of Asphodelus aestivus. All compounds were structurally identified by spectroscopic methods, including UV, MS, and NMR (1D and 2D) spectroscopy. Among the compounds isolated, chlorogenic acid and isoorientin were found to be the main compounds of the methanolic extract.

Summary The structural changes of E. globulus wood extractives during bleaching with chlorine dioxide (D), oxygen (O), ozone (Z) and hydrogen peroxide (P) were studied. The detailed characterisation of the extractive derivatives detected in the partially bleached D, O, P and Z pulps was achieved by performing reactions of pure reference compounds with the different bleaching agents. The results show that the unsaturated sterols and fatty acids are extensively degraded during chlorine dioxide and ozone bleaching and only partially degraded during oxygen and hydrogen peroxide bleaching. The corresponding saturated extractives as well as the long chain aliphatic alcohols and ω-hydroxyfatty acids were stable during bleaching. The main oxidation products of β-sitosterol and oleic and linoleic acids, including one chlorinated derivative of linoleic acid, were identified here for the first time in E. globulus bleached pulps and bleaching filtrates.

Bis(trimethylsilyl) derivative of ethyl 3-aminopyrazole-4-carboxylate (VI) and tris(trimethylsilyl) derivative of ethyl 3,5-diaminopyrazole-4-carboxylate (VII) on reaction with 2,3,5-tri-O-benzoyl-D-ribofuranolyl chloride and subsequent debenzoylation afforded the respective β-D-ribofuranosyl derivatives VIIIa and Xa. Their alkaline hydrolysis led to 1-(β-D-ribofuranosyl)-3-aminopyrazole-4-carboxylic acid (VIIIc) and 1-(β-D-ribofuranosyl)-3,5-diaminopyrazole-4-carboxylic acid (Xb). The esters VIIIa and Xa were not ammonolyzed under normal conditions. Contrary to nucleosidation of the silyl derivatives VI and VII, sodium salt of ethyl 3-aminopyrazole-4-carboxylate was alkylated with 4-chloromethyl-2,2-dimethyl-1,3-dioxolane (XI) or 5-(p-toluenesulfonyloxy)-1,3-dioxane (XVIIb) to give a mixture of the N-isomeric derivatives XIIIa, XIXa and XIIa, XVIIIa, respectively; sodium salt of the 3,5-diamino derivative V reacted with these synthons under formation of the corresponding compounds XIIIb and XXa. Subsequent alkaline and acid hydrolysis of XIIa and XIIIb gave the open-chain analogs of nucleosides XV and XVI. The N-(1,3-dioxan-5-yl) derivatives XVIIIc and XXa resisted acid hydrolysis, giving rise only to carboxylic acids XVIIIb and XXb.

Abstract Besides the known compounds 2,4,6-trihydroxyacetophenone 4-O-β -D-glucopyranoside and syringaresinol 4’-O-β -D-glucopyranoside, the novel sesquiterpenoid 1,2-dehydro-3-oxocostic acid β - D-glucopyranoside ester was isolated from Leontodon tuberosus L. and its structure established by mass spectrometry and 1D- and 2D-NMR spectroscopy. Additionally, a number of fatty and phenolic acids was identified in the crude methanolic extract by HPLC-DAD and HPLC-MS. The chemosystematic impact of the new sesquiterpenoid is discussed briefly.

Bile acid receptors have been identified as important targets for the development of new therapeutics to treat various metabolic and inflammatory diseases. The synthesis of new bile acid analogues can help elucidate structure–activity relationships and define compounds that activate these receptors selectively. Towards this, access to large quantities of a chenodeoxycholic acid derivative bearing a C-12 methyl and a C-13 to C-14 double bond provided an interesting scaffold to investigate the chemical manipulation of the C/D ring junction in bile acids. The reactivity of this alkene substrate with various zinc carbenoid species showed that those generated using the Furukawa methodology achieved selective α-cyclopropanation, whereas those generated using the Shi methodology reacted in an unexpected manner giving rise to a rearranged skeleton whereby the C ring has undergone contraction to form a novel spiro–furan ring system. Further derivatization of the cyclopropanated steroid included O-7 oxidation and epimerization to afford new bile acid derivatives for biological evaluation.

Eleven known triterpenes (α-amyrin, β-amyrin, lupeol, and their respective acetates, 3- O-acetyl derivatives of betulinic, oleanolic, and ursolic acids, cycloartenol, and tirucall-7,24-dienol), two new flavonols presenting an uncommon interglycosidic O-(1→3) linkage (kaempferol 3- O-α-L-arabinofuranosyl-(1→3)-α-L-rhamnoside and quercetin 3- O-α-L-arabinofuranosyl-(1→3)-α-L-rhamnoside), β-sitosterol, stigmasterol, quercetin, and gallic acid were isolated from the Amazonian medicinal mistletoe, Cladocolea micrantha Kuijt (Loranthaceae). Their structures were established by spectral methods and eventual chromatographic comparisons. The quercetin derivative was not cytotoxic to MV3 human melanoma cells, but was able, when administered at 1 μg/mL, to promote a twofold inhibition of the migration of the cells through the transwell system when compared with paclitaxel at 5 μM.

The development of a novel synthesis of acetophenone benzopyran is reported. A acetophenone benzopyran derivative was prepared from 1-(2,4-dihydroxyphenyl)ethanone (3) through O-prenylation and Lewis acids catalyzed intermolecular cyclization reaction. The structure of product 1-(3,4-dihydro-4,4-dimethyl-7-hydroxy-2H-1- benzopyran -6-yl)- ethanone (1) was characterized by UV, IR, 1H-NMR, 13C-NMR and elemental analysis.

Робота присвячена синтезу та дослідженню властивостей ряду нових N-ацил похідних антранілової кислоти. Похідні антранілової кислоти різної хімічної будови, як природного походження, так і синтетичні, привертають увагу дослідників через широкий спектр активності стосовно багатьох грам-позитивних та грам-негативних мікроорганізмів (в тому числі стосовно штамів резистентних до більшості інших антимікробних сполук). Тому ціленаправлений синтез нових сполук шляхом модифікації антранілової кислоти введенням функціональних замісників різної природи та подальше вивчення властивостей й біологічної активності є перспективним напрямком сучасних досліджень. Крім того, проведено визначення чутливості різних морфологічних форм Candida albicans до всіх синтезованих похідних. Показано, що досліджувані синтетичні похідні є більш активними щодо клітин у складі біоплівки, яка складається з дріжджоподібної форми C. albicans, ніж тих клітин, які утворюють біоплівку гіфального типу.
The work is devoted to synthesis of novel N-acyl derivatives of anthranilic acid. The anthranilic acid derivatives of various chemical structures, both natural and synthetic, attract researchers' attention through a wide spectrum of activity in relation to many gram-positive and gram-negative microorganisms (including strains resistant to most other antimicrobial compounds). Therefore, the obtainment of new potent compounds through introduction of various functional substituents into anthranilic acid and further study of properties and biological activity is a promising direction in modern research. In addition, various morphological forms of Candida albicans were tested for its immunity to all synthesized derivatives. It has been shown that the synthetic derivatives studied are more active in relation to cells of the biofilm composition, which consists of the yeast-like form of C. albicans, than those cells that form a hyphal type biofilm.
Работа посвящена синтезу и исследованию свойств ряда новых N-ацил производных антраниловой кислоты. Производные антраниловой кислоты разного химического строения, как природного происхождения, так и синтетические, привлекают внимание исследователей из-за широкого спектра активности в отношении многих грамположительных и грамотрицательных микроорганизмов (в том числе по штаммов резистентных к большинству других антимикробных соединений). Поэтому целенаправленній синтез новых соединений путем модификации антраниловой кислоты введением функциональных заместителей различной природы и дальнейшее изучение свойств и биологической активности является перспективным направлением современных исследований. Кроме того, проведено определение чувствительности различных морфологических форм Candida albicans ко всем синтезированных производных. Показано, что исследуемые синтетические производные являются более активными в отношении клеток в составе биопленки, которая состоит из дрожжеподобные формы C. albicans, чем тех клеток, которые образуют биопленку гифального типа.

The Ph.D. project compiled in this thesis has focused on the role of the solvent in solid-liquid phase equilibria and in nucleation kinetics. Six organic substances have been selected as model compounds, viz. ortho-, meta- and para-hydroxybenzoic acid, salicylamide, meta- and para-aminobenzoic acid. The different types of crystal phases of these compounds have been explored, and their respective solid-state properties have been determined experimentally. The solubility of these crystal phases has been determined in various solvents between 10 and 50 oC. The kinetics of nucleation has been investigated for salicylamide by measuring the metastable zone width, in five different solvents under different experimental conditions. A total of 15 different crystal phases were identified among the six model compounds. Only one crystal form was found for the ortho-substituted compounds, whereas the meta-isomeric compounds crystallized as two unsolvated polymorphs. The para-substituted isomers crystallized as two unsolvated polymorphs and as several solvates in different solvents. It was discovered that the molar solubility of the different crystal phases was linked to the temperature dependence of solubility. In general, a greater molar solubility corresponds to a smaller temperature dependence of solubility. The generality of this relation for organic compounds was investigated using a test set of 41 organic solutes comprising a total of 115 solubility curves. A semi-empirical solubility model was developed based on how thermodynamic properties relate to concentration and temperature. The model was fitted to the 115 solubility curves and used to predict the temperature dependence of solubility. The model allows for entire solubility curves to be constructed in new solvents based on the melting properties of the solute and the solubility in that solvent at a single temperature. Based on the test set comprising the 115 solubility curves it was also found that the melting temperature of the solute can readily be predicted from solubility data in organic solvents. The activity of the solid phase (or ideal solubility) of four of the investigated crystal phases was determined within a rigorous thermodynamic framework, by combining experimental data at the melting temperature and solubility in different solvents and temperatures. The results show that the assumptions normally used in the literature to determine the activity of the solid phase may give rise to errors up to a factor of 12. An extensive variation in the metastable zone width of salicylamide was obtained during repeated experiments performed under identical experimental conditions. Only small or negligible effects on the onset of nucleation were observed by changing the saturation temperature or increasing the solution volume. The onset of nucleation was instead considerably influenced by different cooling rates and different solvents. A correlation was found between the supersaturation ratio at the average onset of nucleation and the viscosity of the solvent divided by the solubility of the solute. The trends suggest that an increased molecular mobility and a higher concentration of the solute reduce the metastable zone width of salicylamide.
QC 20100831

There is a strong interest in phenolic compounds and nitrocompounds in the function of their diverse and significant biological activities. Such compounds can participate in electron transfer reactions and produce metabolites that influence the redox state at the cellular level, with consequent effect on vital biochemical processes. This work aimed to determine the electrodic mechanism involved in the oxidation of bergenin and the reduction of nitrobenzyl derivatives and to evaluate possible supramolecular interactions of bergenin with β-cyclodextrin (β-CD) and deoxyribonucleic acid (DNA) in order to increase its solubility in aqueous medium and help in understanding the molecular mechanism of biological action. The electrochemical studies in protic and aprotic medium were performed in potentiostat PGSTAT302 (AUT 73222) from Autolab® using voltammetric techniques. The influence of the interaction of different cyclodextrins on the solubility of bergenin in aqueous medium was verified through the phase transfer study by cyclic voltammetry. The bergenin:β-CD complex was prepared in 1:1 and 1:2 proportions by the coevaporation technique and characterized by spectroscopic techniques. The theoretical studies were performed through the Gaussian program 09. Bergenin in the free and complexed form were evaluated against antioxidant capacity (lipid peroxidation assays), cytotoxicity (cell viability versus macrophages), and interaction with estimated DNA through the use of dsDNA (double strand) electrochemical sensor and with ssDNA (single strand) for UV-Vis spectrophotometry in solution. The electrochemical results obtained for bergenin demonstrated that its oxidation mechanism in aprotic and protic environments involves, respectively, loss of 1e-/1H+ and 2e-/2H+, when using a glassy carbon electrode. Theoretical data contributed to clarify that oxidative mechanisms involve phenolic hydroxyls. The antioxidant activity of bergenin in the lipoperoxidation inhibition assays was favored in its complexed form with β-CD 1:1. The cytotoxicity of bergenin evaluated in macrophages was also influenced by interaction with β-CD. The electrochemical studies involving ssDNA demonstrated interaction between bergenin and the constituent bases of DNA, suggesting a possible mechanism of biological action. However, the dsDNA biosensor studies showed no interaction. Investigation of the interaction with dsDNA through UV-Vis spectrophotometry resulted in a binding constant between DNA and bergenin in the free and complexed form on the order of 103 and 104 M-1, respectively. The electrochemical behavior of the nitrobenzyl derivatives obtained in aprotic medium presented a voltammetric profile of great complexity, involving patterns related to autoprotonation and dissociative electron transfer reactions. The order of ease of reduction, based on values of first wave reduction potential, was found: ANB > EANBEN > EANB > AANB > ANOH > ATN = ENF > ANBNa > ENM > ANF, obtaining a positive correlation between the compounds with (less negative) with more pronounced biological activity (leishmanicidal and antitumor activities), already described in the literature, which justifies the importance of the electrochemical investigation of bioactive compounds as a tool in medical chemistry, in processes related to the transfer of electrons.
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Há forte interesse a cerca de compostos fenólicos e nitrocompostos em função de suas diversas e significativas atividades biológicas. Tais compostos podem participar de reações de transferência de elétrons e produzir metabólitos que influenciam o estado redox em nível celular, com consequente efeito em processos bioquímicos vitais. Deste modo, este trabalho teve como objetivo determinar o mecanismo eletródico envolvido na oxidação da bergenina e na redução dos derivados nitrobenzílicos e avaliar possíveis interações supramoleculares da bergenina com β-ciclodextrina (β-CD) e ácido desoxirribonucléico (DNA), a fim de aumentar sua solubilidade em meio aquoso e auxiliar no entendimento do mecanismo molecular de ação biológica. Os estudos eletroquímicos em meio prótico e aprótico foram realizados em potenciostato PGSTAT302 (AUT 73222) da Autolab® através de técnicas voltamétricas. A influência da interação de diferentes ciclodextrinas sobre a solubilidade da bergenina em meio aquoso foi verificada através do estudo de transferência de fase por voltametria cíclica. O complexo bergenina:β-CD foi preparado nas proporções 1:1 e 1:2 através da técnica de co-evaporação e caracterizado através de técnicas espectroscópicas. Os estudos teóricos foram realizados através do programa Gaussian 09. A bergenina na forma livre e complexada foram avaliadas frente à capacidade antioxidante (ensaios de peroxidação lipídica), citotoxicidade (viabilidade celular frente a macrófagos), e a interação com DNA estimada através da utilização de sensor eletroquímico de dsDNA (fita dupla) e com ssDNA (fita simples) e espectrofotometria UV-Vis, em solução. Os resultados eletroquímicos obtidos para bergenina demonstraram que seu mecanismo de oxidação em meio aprótico e prótico envolve, respectivamente, a perda de 1e-/1H+ e de 2e-/2H+, ao utilizar eletrodo de carbono vítreo. Os dados teóricos contribuiram para esclarecer que os mecanismos oxidativos envolvem as hidroxilas fenólicas. A atividade antioxidante da bergenina verificada nos ensaios de inibição de lipoperoxidação foi favorecida em sua forma complexada com β-CD na proporção 1:1. A citotoxicidade da bergenina avaliada em macrófagos também sofreu influência da interação com β-CD. Os estudos eletroquímicos envolvendo ssDNA demonstraram interação entre bergenina e as bases constituintes do DNA, sugerindo um possível mecanismo de ação biológico. Já os estudos com biossensor de dsDNA, não demonstraram interação. A investigação da interação com dsDNA através da espectrofotometria UV-Vis resultou numa constante de ligação entre DNA e bergenina na forma livre e complexada na ordem de 103 e 104 M-1, respectivamente. O comportamento eletroquímico dos derivados nitrobezílicos obtidos em meio aprótico apresentaram um perfil voltamétrico de grande complexidade, envolvendo padrões relacionados a reações de autoprotonação e de transferência de elétrons dissociativa. A ordem de facilidade de redução, baseada em valores de potencial de primeira onda de redução, encontrada foi: ANB > EANBEN > EANB > AANB > ANOH > ATN = ENF > ANBNa > ENM > ANF, obtendose correlação positiva entre os compostos com maior potencial de redução (menos negativos) com atividade biológica mais pronunciada (atividades leishmanicida e antitumoral), já descritas na literatura, o que justifica a importância da investigação eletroquímica de compostos bioativos como ferramenta em química medicinal, em processos relacionados à transferência de elétrons.

Doutoramento em Bioquímica
Os polissacarídeos são os componentes maioritários dos grãos de café verde e torrado e da bebida de café. Os mais abundantes são as galactomananas, seguindo-se as arabinogalactanas. Durante o processo de torra, as galactomananas e arabinogalactanas sofrem modificações estruturais, as quais estão longe de estar completamente elucidadas devido à sua diversidade e à complexidade estrutural dos compostos formados. Durante o processo de torra, as galactomananas e arabinogalactanas reagem com proteínas, ácidos clorogénicos e sacarose, originando compostos castanhos de alto peso molecular contendo nitrogénio, designados de melanoidinas. As melanoidinas do café apresentam diversas atividades biológicas e efeitos benéficos para a saúde. No entanto, a sua estrutura exata e os mecanismos envolvidos na sua formação permanecem desconhecidos, bem como a relação estrutura-atividade biológica. A utilização de sistemas modelo e a análise por espectrometria de massa permitem obter uma visão global e, simultaneamente, detalhada das modificações estruturais nos polissacarídeos do café promovidas pela torra, contribuindo para a elucidação das estruturas e mecanismos de formação das melanoidinas. Com base nesta tese, oligossacarídeos estruturalmente relacionados com a cadeia principal das galactomananas, (β1→4)-Dmanotriose (Man3), e as cadeias laterais das arabinogalactanas, (α1→5)-Larabinotriose (Ara3), isoladamente ou em misturas com ácido 5-Ocafeoilquínico (5-CQA), o ácido clorogénico mais abundante nos grãos de café verde, e péptidos compostos por tirosina e leucina, usados como modelos das proteínas, foram sujeitos a tratamento térmico a seco, mimetizando o processo de torra. A oxidação induzida por radicais hidroxilo (HO•) foi também estudada, uma vez que estes radicais parecem estar envolvidos na modificação dos polissacarídeos durante a torra. A identificação das modificações estruturais induzidas por tratamento térmico e oxidativo dos compostos modelo foi feita por estratégias analíticas baseadas principalmente em espectrometria de massa, mas também em cromatografia líquida. A cromatografia de gás foi usada na análise de açúcares neutros e ligações glicosídicas. Para validar as conclusões obtidas com os compostos modelo, foram também analisadas amostras de polissacarídeos do café obtidas a partir de resíduo de café e café instantâneo. Os resultados obtidos a partir dos oligossacarídeos modelo quando submetidos a tratamento térmico (seco), assim como à oxidação induzida por HO• (em solução), indicam a ocorrência de despolimerização, o que está de acordo com estudos anteriores que reportam a despolimerização das galactomananas e arabinogalactanas do café durante a torra. Foram ainda identificados outros compostos resultantes da quebra do anel de açúcares formados durante o tratamento térmico e oxidativo da Ara3. Por outro lado, o tratamento térmico a seco dos oligossacarídeos modelo (individualmente ou quando misturados) promoveu a formação de oligossacarídeos com um maior grau de polimerização, e também polissacarídeos com novos tipos de ligações glicosídicas, evidenciando a ocorrência de polimerização através reações de transglicosilação não enzimática induzidas por tratamento térmico a seco. As reações de transglicosilação induzidas por tratamento térmico a seco podem ocorrer entre resíduos de açúcares provenientes da mesma origem, mas também de origens diferentes com formação de estruturas híbridas, contendo arabinose e manose como observado nos casos dos compostos modelo usados. Os resultados obtidos a partir de amostras do resíduo de café e de café instantâneo sugerem a presença de polissacarídeos híbridos nestas amostras de café processado, corroborando a ocorrência de transglicosilação durante o processo de torra. Além disso, o estudo de misturas contendo diferentes proporções de cada oligossacarídeo modelo, mimetizando regiões do grão de café com composição distinta em polissacarídeos, sujeitos a diferentes períodos de tratamento térmico, permitiu inferir que diferentes estruturas híbridas e não híbridas podem ser formadas a partir das arabinogalactanas e galactomananas, dependendo da sua distribuição nas paredes celulares do grão e das condições de torra. Estes resultados podem explicar a heterogeneidade de estruturas de melanoidinas formadas durante a torra do café. Os resultados obtidos a partir de misturas modelo contendo um oligossacarídeo (Ara3 ou Man3) e 5-CQA sujeitas a tratamento térmico a seco, assim como de amostras provenientes do resíduo de café, mostraram a formação de compostos híbridos compostos por moléculas de CQA ligadas covalentemente a um número variável de resíduos de açúcar. Além disso, os resultados obtidos a partir da mistura contendo Man3 e 5-CQA mostraram que o CQA atua como catalisador das reações de transglicosilação. Por outro lado, nas misturas modelo contendo um péptido, mesmo contendo também 5-CQA e sujeitas ao mesmo tratamento, observou-se uma diminuição na extensão das reações transglicosilação. Este resultado pode explicar a baixa extensão das reações de transglicosilação não enzimáticas durante a torra nas regiões do grão de café mais ricas em proteínas, apesar dos polissacarídeos serem os componentes maioritários dos grãos de café. A diminuição das reações de transglicosilação na presença de péptidos/proteínas pode dever-se ao facto de os resíduos de açúcares redutores reagirem preferencialmente com os grupos amina de péptidos/proteínas por reação de Maillard, diminuindo o número de resíduos de açúcares redutores disponíveis para as reações de transglicosilação. Além dos compostos já descritos, uma diversidade de outros compostos foram formados a partir dos sistemas modelo, nomeadamente derivados de desidratação formados durante o tratamento térmico a seco. Em conclusão, a tipificação das modificações estruturais promovidas pela torra nos polissacarídeos do café abre o caminho para a compreensão dos mecanismos de formação das melanoidinas e da relação estrutura-atividade destes compostos.
Polysaccharides are the major components of green and roasted coffee beans, and coffee brew. The most abundant ones are galactomannans, followed by arabinogalactans. During the roasting process, galactomannans and arabinogalactans undergo structural modifications that are far to be completely elucidated due to their diversity and complexity of the compounds formed. During the roasting process, galactomannans and arabinogalactans react with proteins, chlorogenic acids, and sucrose, originating high molecular weight brown compounds containing nitrogen, known as melanoidins. Several biological activities and beneficial health effects have been attributed to coffee melanoidins. However, their exact structures and the mechanisms involved in their formation remain unknown, as well as the structure-biological activity relationship. The use of model systems and mass spectrometry analysis allow to obtain an overall view and, simultaneously, detailed, of the structural modifications in coffee polysaccharides promoted by roasting, contributing to the elucidation of the structures and formation mechanisms of melanoidins. Based on this thesis, oligosaccharides structurally related to the backbone of galactomannans, (β1→4)-D-mannotriose, and the side chains of arabinogalactans, (α1→5)-Larabinotriose, alone or in mixtures with 5-O-caffeoylquinic acid, the most abundant chlorogenic acid in green coffee beans, and dipeptides composed by tyrosine and leucine, used as models of proteins, were submitted to dry thermal treatments, mimicking the coffee roasting process. The oxidation induced by hydroxyl radicals (HO•) was also studied, since these radicals seem to be involved in the modification of the polysaccharides during roasting. The identification of the structural modifications induced by thermal and oxidative treatment of the model compounds was performed mostly by mass spectrometry-based analytical strategies, but also using liquid chromatography. Gas chromatography was used in the analysis of neutral sugars and glycosidic linkages. To validate the conclusions achieved with the model compounds, coffee polysaccharide samples obtained from spent coffee grounds and instant coffee were also analysed. The results obtained from the model oligosaccharides when submitted to thermal treatment (dry) or oxidation induced by HO• (in solution) indicate the occurrence of depolymerization, which is in line with previous studies reporting the depolymerization of coffee galactomannans and arabinogalactans during roasting. Compounds resulting from sugar ring cleavage were also formed during thermal treatment and oxidative treatment of Ara3. On the other hand, the dry thermal treatment of the model oligosaccharides (alone or when mixed) promoted the formation of oligosaccharides with a higher degree of polymerization, and also polysaccharides with new type of glycosidic linkages, evidencing the occurrence of polymerization via non-enzymatic transglycosylation reactions induced by dry thermal treatment. The transglycosylation reactions induced by dry thermal treatment can occur between sugar residues from the same origin, but also of different origins, with formation of hybrid structures, containing arabinose and mannose in the case of the model compounds used. The results obtained from spent coffee grounds and instant coffee samples suggest the presence of hybrid polysaccharides in these processed coffee samples, corroborating the occurrence of transglycosylation during the roasting process. Furthermore, the study of mixtures containing different proportions of each model oligosaccharide, mimicking coffee bean regions with distinct polysaccharide composition, subjected to different periods of thermal treatment, allowed to infer that different hybrid and non-hybrid structures may be formed from arabinogalactans and galactomannans, depending on their distribution in the bean cell walls and on roasting conditions. These results may explain the heterogeneity of melanoidins structures formed during coffee roasting. The results obtained from model mixtures containing an oligosaccharide (Ara3 or Man3) and 5-CQA and subjected to dry thermal treatment, as well as samples derived from spent coffee grounds, showed the formation of hybrid compounds composed by CQA molecules covalently linked to a variable number of sugar residues. Moreover, the results obtained from the mixture containing Man3 and 5-CQA showed that CQA acts as catalyst of transglycosylation reactions. On the other hand, in the model mixtures containing a peptide, even if containing 5-CQA and subjected to the same treatment, it was observed a decrease in the extent of transglycosylation reactions. This outcome can explain the low extent of non-enzymatic transglycosylation reactions during roasting in coffee bean regions enriched in proteins, although polysaccharides are the major components of the coffee beans. The decrease of transglycosylation reactions in the presence of peptides/proteins can be related with the preferential reactivity of reducing residues with the amino groups of peptides/proteins by Maillard reaction, decreasing the number of reducing residues available to be directly involved in the transglycosylation reactions. In addition to the compounds already described, a diversity of other compounds were formed from model systems, namely dehydrated derivatives formed during dry thermal treatment. In conclusion, the identification of the structural modifications in coffee polysaccharides promoted by roasting pave the way to the understanding of the mechanisms of formation of melanoidins and structure-activity relationship of these compounds.

Quercetin-3-O-glucoside (Q3G), a glycosylated derivative of quercetin, is a polyphenolic compound known to possess diverse biological activities. Its moderately hydrophilic nature is a critical factor governing the accessibility to the active sites of oxidative damages in vivo. It was hypothesized that biological activities of Q3G can be further enhanced by regioselective acylation with fatty acids which gives more lipophilicity. Q3G was acylated with six selected long chain fatty acids: stearic acid, oleic acid, linoleic acid, ?-linolenic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), using Candida antactica lipase. The derivatives were evaluated for their potential in inhibiting lipid oxidation in food systems and human low density lipoprotein (LDL), and cytoprotection and anti-inflammatory effect in cell culture model systems. The fatty acid derivatives of Q3G possessed greater effectiveness in inhibiting lipid oxidation in oil-in-water emulsions, and better cytoprotective effect against H2O2- and cigarette smoke toxicant-induced cytotoxicity when compared to Q3G.

Six long chain fatty acid esters of quercetin-3-O-glucoside (Q3G) acylated enzymatically were used for determining their antiproliferative action in comparison to precursor compounds (quercetin, Q3G and six fatty acids namely, stearic acid, oleic acid, linoleic acid, alpha-linolenic acid, eicosapentaenoic and docosahexanoic acids) using HepG2 cells. Long chain fatty acid esters of Q3G showed significant inhibition of cell proliferation (approximately 85% to 90%) compared to the precursor compounds and two prescribed anticancer-drugs (Sorafenib and Cisplatin) after 6 hrs and 24 hrs by inducing cell cycle arrest, apoptosis and DNA topoisomerase II inhibition. Among the six fatty acid esters of Q3G, oleic acid ester (OA-Q3G) displayed the greatest anti-proliferation action and upon further investigation showed significant regulation of expression of genes involved in cell cycle, growth, survival and apoptosis at gene and protein level. Overall, results of the study suggest strong potential of these novel compounds in treatment of liver cancer.