XXIV Congresso de Iniciação Científica da Unicamp, 2016
Resumo O projeto consiste em um estudo realizado com os frutos Mangostin (Garcinia mangostana) e ... more Resumo O projeto consiste em um estudo realizado com os frutos Mangostin (Garcinia mangostana) e Pitaia (Hylocereus sp.) afim de encontrar novas moléculas de importância farmacêutica para a Doença de Alzheimer. Realizou-se uma comparação com a mangiferina, composto natural bioativo que foi originalmente isolado das folhas de Manga (Mangifera indica L.), o qual possui atividade biológica bastante ampla. Sabe-se pela literatura que estes frutos são ricos em xantonas e que a mangiferina é composta pelo C-glicosídeo da xantona noratriol¹, portanto, este estudo leva em consideração estas semelhanças estruturais para encontrar atividades farmacológicas em produtos naturais.
Anais do Congresso de Iniciação Científica da Unicamp
A β-secretase (BACE-1) é uma enzima que hidrolisa a proteína precursora do amiloide (PPA), dando ... more A β-secretase (BACE-1) é uma enzima que hidrolisa a proteína precursora do amiloide (PPA), dando origem a oligopeptídeos. Estes apresentam propriedades auto-agregantes, levando à formação de oligômeros tóxicos e às placas amiloides. Este processo de clivagem da PPA, conhecido como via amiloidogênica, é uma importante característica da doença de Alzheimer (DA). O projeto dedica-se à síntese e caracterização de chalconas derivadas da 2'aminoacetofenona, com diferentes padrões de substituição no anel A (Figura 1), para estudar o seu efeito inibitório sob atividade da β-secretase.
Candidiasis is recognized worldwide as an opportunistic infection. The severities of the infectio... more Candidiasis is recognized worldwide as an opportunistic infection. The severities of the infection increase in immunosuppression conditions with possible occurrence of visceral mycoses and sometimes are widespread and systemic. Increased resistance in strains of Candida albicans is a major obstacle to antifungal therapy. The aim of this study was to correlate the chemical structure of compounds with experimental data from biological activity anti-Candida albicans. We performed classical QSAR for a series of twenty derivatives of ketone -β unsaturated against resistant strains of Candida albicans. Ninety-four descriptors were calculated and multiparameter model was obtained through Partial Least Squares (PLS) method. The results showed that thermodynamic, dimensional and steric parameters are important in elucidating of action mechanism compounds. Four descriptors (molar refractivity, ionization potential, molecular length and Verloop B4) were selected and good model (n= 20; R2 = 0....
O objetivo do presente trabalho foi identificar os principais descritores dos derivados analogos ... more O objetivo do presente trabalho foi identificar os principais descritores dos derivados analogos de chalcona com intuito de correlacionar com a atividade anti-Candida albicans. A incidencia de infeccoes sistemicas por C. albicans vem crescendo bastante nos ultimos anos, particularmente nos casos de HIV e tambem em funcao do aumento da resistencia ao arsenal terapeutico existente. Realizamos um estudo QSAR-2D, obtendo um modelo multidimensional pelo metodo PLS. O modelo obtido possui quatro descritores: refratividade molar, potencial de ionizacao, comprimento molecular e Verloop B4(A). Com apenas 3 variaveis latentes (PCs), foi capaz de acumular 96,14% da informacao original, elucidando 85% da variância total e predizendo 78% da atividade biologica. O modelo proposto possui bom grau de ajuste e significância estatistica (R = 0,776 e SEC = 0,229). Os metodos LOO cross-validation, LNO cross-validation, Y-randomization e a validacao externa indicaram que o modelo e significante, robusto...
Background: Alzheimer's disease (AD) is an irreversible and progressive neurodegeneration, wi... more Background: Alzheimer's disease (AD) is an irreversible and progressive neurodegeneration, with a multifactorial pathophysiology, including cholinergic deficit, amyloid plaques, neurofibrillary tangles, oxidative stress, and neurodegeneration. Despite the severity of the disease, the therapeutic arsenal is limited, arousing the interest of researchers to search for substances that can act on these markers. Objective: In this review, we highlight some relevant points: the ability of chalcones to act on different targets related to the pathophysiology of Alzheimer's disease: cholinesterases, amyloid peptide, beta-secretase and other biomarkers. Method: This mini-review covered the literature concerning chalcones bioactivity from 2010 until now. In addition to the theoretical review, we included the prediction of physicochemical properties, using SwissADME software. Results: We found that the majority of the chalcones have been tested against cholinesterases, with moderate to g...
In this work, we have obtained eleven acyl-hydrazones derived from isoniazid, and three from subs... more In this work, we have obtained eleven acyl-hydrazones derived from isoniazid, and three from substituted benzhydrazide.The effect of these compounds on acetylcholinesterase (AChE) was evaluated and benzydrazide derivatives were more effective in inhibiting AChE. Among the isoniazid derivatives, those having a benzodioxol or dihydroxyl groups are the most potent. The antioxidant activity was also studied. In silico studies of pharmacokinetic (PK) properties of the synthesized compounds suggests that all of them are able to cross the blood brain barrier (BBB). They are predicted to have high gastrointestinal abosrption (GI).
Alzheimer’s disease (AD) is related to the anomalous binding that occurs between amyloid-β peptid... more Alzheimer’s disease (AD) is related to the anomalous binding that occurs between amyloid-β peptide (Aβ) and copper ion, through imidazole ring of histidine (His), as stated in the literature. It is also known that high-affinity metal ion chelators can be pharmacologically used as a possible therapeutic approach. In this work, we tested the ability “in vitro” of chitosan (Chi) to reduce Aβ aggregation and Thioflavin T binding assay indicated that chitosan has affinity for Aβ and interferes in its aggregation. We also tested the ability of Chi to uptake copper ions in the presence of Aβ or His. Equilibrium data reveals that chitosan acted as an effective chelating agent competing with Aβ and histidine for copper binding. The addition of histidine or Aβ in the system promotes an unfolding of chitosan chains, as verified by small-angle X-ray scattering. Extended X-ray absorption fine structure and XPS spectra show that new copper interactions with groups containing nitrogen in the presence of histidine may occur. These results can help understanding fundamental chemical interactions among species detected in AD and biopolymers, opening up possibilities for new treatment approaches for this disease.
Revista dos Trabalhos de Iniciação Científica da UNICAMP
Dando continuidade à linha de pesquisa do grupo, o projeto envolve o planejamento de fármacos e s... more Dando continuidade à linha de pesquisa do grupo, o projeto envolve o planejamento de fármacos e síntese orgânica, Estudos de docking molecularforam realizados para predizer interação de moléculas contendo as subunidades desejadas com diversas variações, com a enzima Acetilcolinesterase. Uma vez selecionadas, as moléculas candidatas foram sintetizadas em laboratório e testadas em ensaios de inibição enzimática.
Abstract Indoline is an important structural motif present in several biologically active compoun... more Abstract Indoline is an important structural motif present in several biologically active compounds from both natural and synthetic origins. The occurrence of this heterocyclic unity in these compounds is closely related to the biological activities they exhibit. This fact stimulated efforts that have been made worldwide to develop new synthetic approaches to prepare indolines. In this paper we reviewed critically the methods for indoline synthesis developed in the last years (from 2010 to 2018).
A pentafluorobenzamide stationary phase was synthesized by an easy method with no intermediate pu... more A pentafluorobenzamide stationary phase was synthesized by an easy method with no intermediate purification steps. Physicochemical characterization (elemental analysis, Fourier transform infrared, Si and C nuclear magnetic resonance) confirmed the presence of pentafluorobenzamide functionalization on the surface of the silica particles. The pentafluorobenzamide stationary phase proved to be quite versatile as it can be used in two different modes in liquid chromatography: reversed phase and hydrophilic interaction liquid chromatography. Chromatographic characterizations in both modes confirmed the multiple interactions established by the new stationary phase, such as hydrogen bonding and π-π and ion-exchange interactions. The pentafluorobenzamide stationary phase was successfully employed for the separation of nucleosides and antihypertensive drugs under hydrophilic interaction liquid chromatography conditions, as well as pesticides and benzodiazepine using reversed phase conditions...
Alzheimer's disease is a progressive and neurodegenerative disorder of the CNS, affecting eld... more Alzheimer's disease is a progressive and neurodegenerative disorder of the CNS, affecting elderly people. The current pharmacological approach is based on the improvement of cholinergic neurotransmission by inhibiting acetylcholinesterase (AChE) with AChE inhibitors. The disease is also characterized by the accelerated accumulation of β-amyloid plaques around neurons. Furthermore, in vitro studies revealed that AChE can induce β-amyloid peptide (Aβ) aggregation. Computer-aided molecular design by virtual screening was here employed to discover novel potential AChE inhibitors, with antifibrillogenic properties, in other words, inhibiting Aβ aggregation. Compounds 1, 4 and 6 showed interesting AChE inhibition. In addition, they particularly inhibit Aβ aggregation in vitro, indicating to be promising novel anti-Alzheimer agents.
Alzheimer's disea... more Alzheimer's disease (AD) is the most common type of dementia and related to the degeneration of hippocampal cholinergic neurons, which dramatically affects cognitive ability. Acetylcholinesterase (AChE) inhibitors are employed as drugs for AD therapy. Three series of sulfonylhydrazone compounds were designed, and their ability to inhibit AChE was evaluated. Fifteen compounds were synthesized and twelve of them had IC50 values of 0.64-51.09 μM. The preliminary structure-activity relationships indicated that the methylcatechol moiety and arylsulfonyl substituents generated better compounds than both the benzodioxole and alkylsulfonyl chains. Molecular dynamics studies of compound 6d showed that the interaction with the peripheral binding site of AChE was similar to donepezil, which may explain its low IC50 (0.64 μM). Furthermore, the drug-likeness of 6d suggests that the compound may have appropriate oral absorption and brain penetration. Compound 6d also presented antiradical activity and was not cytotoxic to LL24 cells, suggesting that this compound might be considered safe. Our findings indicate that arylsulfonylhydrazones may be a promising scaffold for the design of new drug candidates for the treatment of AD.
2-Aminothiazolines share an isosteric relationship with imidazolines and oxazolines with antihype... more 2-Aminothiazolines share an isosteric relationship with imidazolines and oxazolines with antihypertensive activity mainly mediated by the imidazoline I1-receptor. In the present work, we have prepared five aminothiazolines, following a previously described synthetic pathway. Aminothiazolines derived from dicyclopropylmethylamine (ATZ1) and cyclohexylamine (3) are unprecedented in the literature. Competitive radioligand assay was carried out with all synthetic compounds, and the I1 receptor affinity in comparison to rilmenidine in PC12 cells was determined. Surprisingly, the rilmenidine isoster (ATZ1) showed no I1-receptor interaction. Diethyl (ATZ4) and 2-ethyl-hexylamine (ATZ5) derivatives bind to the receptor with 11.98 and 10.94 nmol/l, respectively. These compounds were selected for in vivo experiments. Both compounds reduced the blood pressure of spontaneously hypertensive rats (SHR). The hypotensive effect of these compounds was abrogated in the presence of α2 adrenergic (yohi...
Seven new 4-thiazolidinones bearing the morpholino moiety were easily synthesized by one-pot reac... more Seven new 4-thiazolidinones bearing the morpholino moiety were easily synthesized by one-pot reactions of 4-(2-aminoethyl)morpholine (2-morpholinoethylamine), arenealdehydes and mercaptoacetic acid refluxing toluene for 19 h with moderate to good yields (45-97%). These novel compounds were fully identified and characterized by NMR spectroscopy and mass spectrometry. Thiazolidin-4-ones in vivo anti-inflammatory activities were determined using a croton oil-induced ear edema model of inflammation in BALB C mice. The best results were found for compounds 4c (49.20 mmol/kg), 4d (49.20 mmol/kg) and 4f (52.48 mmol/kg), which showed the ability to decrease the ear edema in mice by 50%, 48% and 54%, respectively, when compared to the standard drug indomethacin. In addition, the in vitro cytotoxicity activity of thiazolidin-4-ones against Vero cells was also performed and four compounds (4a, 4c, 4d and 4f) showed no toxic effect at 500 μg/mL. A docking simulation of compounds into the 1Q4G (COX-1) and 4PH9 (COX-2) enzymes binding site was conducted. This preliminary result will guide us in for further studies to improve the anti-inflammatory activity.
Glutathione (GSH) and related enzymes are pivotal for the normal functioning of several important... more Glutathione (GSH) and related enzymes are pivotal for the normal functioning of several important biological processes. In this review we discuss the biosynthesis and the catalytic cycles of glutathione as well as the major GSH-related enzymes. We also present how glutathione and enzymes are involved in cancer and the chromatographic and non-chromatographic methods used to analyze glutathione and/or its derivatives.
In the title hydrate, C14H13N3O·H2O, the C=N double bond adopts anEconformation and the dihedral ... more In the title hydrate, C14H13N3O·H2O, the C=N double bond adopts anEconformation and the dihedral angle between the aromatic rings is 16.36 (10)°. In the crystal, N—H...O, O—H...O and O—H...N hydrogen bonds link the components into (001) sheets.
Journal of enzyme inhibition and medicinal chemistry, 2016
Acetylcholinesterase inhibitors and compounds that trigger Aβ amyloid oligomerization and fibrill... more Acetylcholinesterase inhibitors and compounds that trigger Aβ amyloid oligomerization and fibrillization represent an opportunity to discover new drug candidates to treat Alzheimer's disease. In this work, we synthesized nine new acylhydrazones and a known one, both employing 3-carboethoxy-4-quinolone derivatives as starting materials with chemical yields ranging from 63% to 90%. We evaluated the effect of these compounds on the acetylcholinesterase (AChE) activity and the fibrillization of Aβ42 peptide. Except for one acylhydrazone, the compounds exhibited good inhibitory effect on AChE (1.2 μM < IC50…
XXIV Congresso de Iniciação Científica da Unicamp, 2016
Resumo O projeto consiste em um estudo realizado com os frutos Mangostin (Garcinia mangostana) e ... more Resumo O projeto consiste em um estudo realizado com os frutos Mangostin (Garcinia mangostana) e Pitaia (Hylocereus sp.) afim de encontrar novas moléculas de importância farmacêutica para a Doença de Alzheimer. Realizou-se uma comparação com a mangiferina, composto natural bioativo que foi originalmente isolado das folhas de Manga (Mangifera indica L.), o qual possui atividade biológica bastante ampla. Sabe-se pela literatura que estes frutos são ricos em xantonas e que a mangiferina é composta pelo C-glicosídeo da xantona noratriol¹, portanto, este estudo leva em consideração estas semelhanças estruturais para encontrar atividades farmacológicas em produtos naturais.
Anais do Congresso de Iniciação Científica da Unicamp
A β-secretase (BACE-1) é uma enzima que hidrolisa a proteína precursora do amiloide (PPA), dando ... more A β-secretase (BACE-1) é uma enzima que hidrolisa a proteína precursora do amiloide (PPA), dando origem a oligopeptídeos. Estes apresentam propriedades auto-agregantes, levando à formação de oligômeros tóxicos e às placas amiloides. Este processo de clivagem da PPA, conhecido como via amiloidogênica, é uma importante característica da doença de Alzheimer (DA). O projeto dedica-se à síntese e caracterização de chalconas derivadas da 2'aminoacetofenona, com diferentes padrões de substituição no anel A (Figura 1), para estudar o seu efeito inibitório sob atividade da β-secretase.
Candidiasis is recognized worldwide as an opportunistic infection. The severities of the infectio... more Candidiasis is recognized worldwide as an opportunistic infection. The severities of the infection increase in immunosuppression conditions with possible occurrence of visceral mycoses and sometimes are widespread and systemic. Increased resistance in strains of Candida albicans is a major obstacle to antifungal therapy. The aim of this study was to correlate the chemical structure of compounds with experimental data from biological activity anti-Candida albicans. We performed classical QSAR for a series of twenty derivatives of ketone -β unsaturated against resistant strains of Candida albicans. Ninety-four descriptors were calculated and multiparameter model was obtained through Partial Least Squares (PLS) method. The results showed that thermodynamic, dimensional and steric parameters are important in elucidating of action mechanism compounds. Four descriptors (molar refractivity, ionization potential, molecular length and Verloop B4) were selected and good model (n= 20; R2 = 0....
O objetivo do presente trabalho foi identificar os principais descritores dos derivados analogos ... more O objetivo do presente trabalho foi identificar os principais descritores dos derivados analogos de chalcona com intuito de correlacionar com a atividade anti-Candida albicans. A incidencia de infeccoes sistemicas por C. albicans vem crescendo bastante nos ultimos anos, particularmente nos casos de HIV e tambem em funcao do aumento da resistencia ao arsenal terapeutico existente. Realizamos um estudo QSAR-2D, obtendo um modelo multidimensional pelo metodo PLS. O modelo obtido possui quatro descritores: refratividade molar, potencial de ionizacao, comprimento molecular e Verloop B4(A). Com apenas 3 variaveis latentes (PCs), foi capaz de acumular 96,14% da informacao original, elucidando 85% da variância total e predizendo 78% da atividade biologica. O modelo proposto possui bom grau de ajuste e significância estatistica (R = 0,776 e SEC = 0,229). Os metodos LOO cross-validation, LNO cross-validation, Y-randomization e a validacao externa indicaram que o modelo e significante, robusto...
Background: Alzheimer's disease (AD) is an irreversible and progressive neurodegeneration, wi... more Background: Alzheimer's disease (AD) is an irreversible and progressive neurodegeneration, with a multifactorial pathophysiology, including cholinergic deficit, amyloid plaques, neurofibrillary tangles, oxidative stress, and neurodegeneration. Despite the severity of the disease, the therapeutic arsenal is limited, arousing the interest of researchers to search for substances that can act on these markers. Objective: In this review, we highlight some relevant points: the ability of chalcones to act on different targets related to the pathophysiology of Alzheimer's disease: cholinesterases, amyloid peptide, beta-secretase and other biomarkers. Method: This mini-review covered the literature concerning chalcones bioactivity from 2010 until now. In addition to the theoretical review, we included the prediction of physicochemical properties, using SwissADME software. Results: We found that the majority of the chalcones have been tested against cholinesterases, with moderate to g...
In this work, we have obtained eleven acyl-hydrazones derived from isoniazid, and three from subs... more In this work, we have obtained eleven acyl-hydrazones derived from isoniazid, and three from substituted benzhydrazide.The effect of these compounds on acetylcholinesterase (AChE) was evaluated and benzydrazide derivatives were more effective in inhibiting AChE. Among the isoniazid derivatives, those having a benzodioxol or dihydroxyl groups are the most potent. The antioxidant activity was also studied. In silico studies of pharmacokinetic (PK) properties of the synthesized compounds suggests that all of them are able to cross the blood brain barrier (BBB). They are predicted to have high gastrointestinal abosrption (GI).
Alzheimer’s disease (AD) is related to the anomalous binding that occurs between amyloid-β peptid... more Alzheimer’s disease (AD) is related to the anomalous binding that occurs between amyloid-β peptide (Aβ) and copper ion, through imidazole ring of histidine (His), as stated in the literature. It is also known that high-affinity metal ion chelators can be pharmacologically used as a possible therapeutic approach. In this work, we tested the ability “in vitro” of chitosan (Chi) to reduce Aβ aggregation and Thioflavin T binding assay indicated that chitosan has affinity for Aβ and interferes in its aggregation. We also tested the ability of Chi to uptake copper ions in the presence of Aβ or His. Equilibrium data reveals that chitosan acted as an effective chelating agent competing with Aβ and histidine for copper binding. The addition of histidine or Aβ in the system promotes an unfolding of chitosan chains, as verified by small-angle X-ray scattering. Extended X-ray absorption fine structure and XPS spectra show that new copper interactions with groups containing nitrogen in the presence of histidine may occur. These results can help understanding fundamental chemical interactions among species detected in AD and biopolymers, opening up possibilities for new treatment approaches for this disease.
Revista dos Trabalhos de Iniciação Científica da UNICAMP
Dando continuidade à linha de pesquisa do grupo, o projeto envolve o planejamento de fármacos e s... more Dando continuidade à linha de pesquisa do grupo, o projeto envolve o planejamento de fármacos e síntese orgânica, Estudos de docking molecularforam realizados para predizer interação de moléculas contendo as subunidades desejadas com diversas variações, com a enzima Acetilcolinesterase. Uma vez selecionadas, as moléculas candidatas foram sintetizadas em laboratório e testadas em ensaios de inibição enzimática.
Abstract Indoline is an important structural motif present in several biologically active compoun... more Abstract Indoline is an important structural motif present in several biologically active compounds from both natural and synthetic origins. The occurrence of this heterocyclic unity in these compounds is closely related to the biological activities they exhibit. This fact stimulated efforts that have been made worldwide to develop new synthetic approaches to prepare indolines. In this paper we reviewed critically the methods for indoline synthesis developed in the last years (from 2010 to 2018).
A pentafluorobenzamide stationary phase was synthesized by an easy method with no intermediate pu... more A pentafluorobenzamide stationary phase was synthesized by an easy method with no intermediate purification steps. Physicochemical characterization (elemental analysis, Fourier transform infrared, Si and C nuclear magnetic resonance) confirmed the presence of pentafluorobenzamide functionalization on the surface of the silica particles. The pentafluorobenzamide stationary phase proved to be quite versatile as it can be used in two different modes in liquid chromatography: reversed phase and hydrophilic interaction liquid chromatography. Chromatographic characterizations in both modes confirmed the multiple interactions established by the new stationary phase, such as hydrogen bonding and π-π and ion-exchange interactions. The pentafluorobenzamide stationary phase was successfully employed for the separation of nucleosides and antihypertensive drugs under hydrophilic interaction liquid chromatography conditions, as well as pesticides and benzodiazepine using reversed phase conditions...
Alzheimer's disease is a progressive and neurodegenerative disorder of the CNS, affecting eld... more Alzheimer's disease is a progressive and neurodegenerative disorder of the CNS, affecting elderly people. The current pharmacological approach is based on the improvement of cholinergic neurotransmission by inhibiting acetylcholinesterase (AChE) with AChE inhibitors. The disease is also characterized by the accelerated accumulation of β-amyloid plaques around neurons. Furthermore, in vitro studies revealed that AChE can induce β-amyloid peptide (Aβ) aggregation. Computer-aided molecular design by virtual screening was here employed to discover novel potential AChE inhibitors, with antifibrillogenic properties, in other words, inhibiting Aβ aggregation. Compounds 1, 4 and 6 showed interesting AChE inhibition. In addition, they particularly inhibit Aβ aggregation in vitro, indicating to be promising novel anti-Alzheimer agents.
Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disea... more Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (AD) is the most common type of dementia and related to the degeneration of hippocampal cholinergic neurons, which dramatically affects cognitive ability. Acetylcholinesterase (AChE) inhibitors are employed as drugs for AD therapy. Three series of sulfonylhydrazone compounds were designed, and their ability to inhibit AChE was evaluated. Fifteen compounds were synthesized and twelve of them had IC50 values of 0.64-51.09 μM. The preliminary structure-activity relationships indicated that the methylcatechol moiety and arylsulfonyl substituents generated better compounds than both the benzodioxole and alkylsulfonyl chains. Molecular dynamics studies of compound 6d showed that the interaction with the peripheral binding site of AChE was similar to donepezil, which may explain its low IC50 (0.64 μM). Furthermore, the drug-likeness of 6d suggests that the compound may have appropriate oral absorption and brain penetration. Compound 6d also presented antiradical activity and was not cytotoxic to LL24 cells, suggesting that this compound might be considered safe. Our findings indicate that arylsulfonylhydrazones may be a promising scaffold for the design of new drug candidates for the treatment of AD.
2-Aminothiazolines share an isosteric relationship with imidazolines and oxazolines with antihype... more 2-Aminothiazolines share an isosteric relationship with imidazolines and oxazolines with antihypertensive activity mainly mediated by the imidazoline I1-receptor. In the present work, we have prepared five aminothiazolines, following a previously described synthetic pathway. Aminothiazolines derived from dicyclopropylmethylamine (ATZ1) and cyclohexylamine (3) are unprecedented in the literature. Competitive radioligand assay was carried out with all synthetic compounds, and the I1 receptor affinity in comparison to rilmenidine in PC12 cells was determined. Surprisingly, the rilmenidine isoster (ATZ1) showed no I1-receptor interaction. Diethyl (ATZ4) and 2-ethyl-hexylamine (ATZ5) derivatives bind to the receptor with 11.98 and 10.94 nmol/l, respectively. These compounds were selected for in vivo experiments. Both compounds reduced the blood pressure of spontaneously hypertensive rats (SHR). The hypotensive effect of these compounds was abrogated in the presence of α2 adrenergic (yohi...
Seven new 4-thiazolidinones bearing the morpholino moiety were easily synthesized by one-pot reac... more Seven new 4-thiazolidinones bearing the morpholino moiety were easily synthesized by one-pot reactions of 4-(2-aminoethyl)morpholine (2-morpholinoethylamine), arenealdehydes and mercaptoacetic acid refluxing toluene for 19 h with moderate to good yields (45-97%). These novel compounds were fully identified and characterized by NMR spectroscopy and mass spectrometry. Thiazolidin-4-ones in vivo anti-inflammatory activities were determined using a croton oil-induced ear edema model of inflammation in BALB C mice. The best results were found for compounds 4c (49.20 mmol/kg), 4d (49.20 mmol/kg) and 4f (52.48 mmol/kg), which showed the ability to decrease the ear edema in mice by 50%, 48% and 54%, respectively, when compared to the standard drug indomethacin. In addition, the in vitro cytotoxicity activity of thiazolidin-4-ones against Vero cells was also performed and four compounds (4a, 4c, 4d and 4f) showed no toxic effect at 500 μg/mL. A docking simulation of compounds into the 1Q4G (COX-1) and 4PH9 (COX-2) enzymes binding site was conducted. This preliminary result will guide us in for further studies to improve the anti-inflammatory activity.
Glutathione (GSH) and related enzymes are pivotal for the normal functioning of several important... more Glutathione (GSH) and related enzymes are pivotal for the normal functioning of several important biological processes. In this review we discuss the biosynthesis and the catalytic cycles of glutathione as well as the major GSH-related enzymes. We also present how glutathione and enzymes are involved in cancer and the chromatographic and non-chromatographic methods used to analyze glutathione and/or its derivatives.
In the title hydrate, C14H13N3O·H2O, the C=N double bond adopts anEconformation and the dihedral ... more In the title hydrate, C14H13N3O·H2O, the C=N double bond adopts anEconformation and the dihedral angle between the aromatic rings is 16.36 (10)°. In the crystal, N—H...O, O—H...O and O—H...N hydrogen bonds link the components into (001) sheets.
Journal of enzyme inhibition and medicinal chemistry, 2016
Acetylcholinesterase inhibitors and compounds that trigger Aβ amyloid oligomerization and fibrill... more Acetylcholinesterase inhibitors and compounds that trigger Aβ amyloid oligomerization and fibrillization represent an opportunity to discover new drug candidates to treat Alzheimer's disease. In this work, we synthesized nine new acylhydrazones and a known one, both employing 3-carboethoxy-4-quinolone derivatives as starting materials with chemical yields ranging from 63% to 90%. We evaluated the effect of these compounds on the acetylcholinesterase (AChE) activity and the fibrillization of Aβ42 peptide. Except for one acylhydrazone, the compounds exhibited good inhibitory effect on AChE (1.2 μM < IC50…
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