Hortensia Rodriguez | Yachay Tech (original) (raw)
Papers by Hortensia Rodriguez
Peptides 2015, Proceedings of the 24th American Peptide Symposium, 2015
The discovery and development of natural, synthetic or peptidomimetic cell-penetrating peptides (... more The discovery and development of natural, synthetic or peptidomimetic cell-penetrating peptides (CPPs) is a promising breakthrough to achieve non-invasive delivery of non-permeable biomolecules in the intracellular compartment. The CPPs are able to carry small molecules, plasmid DNA, interfering RNA, proteins, viruses, nanoparticles among others, across the cellular membrane, resulting in internalization of the intact cargos. In general, are sequence with 5-30 aminoacids, which are classified in cationics, amphipathics or hydrophobics, depending on its structural characteristics. The present review explores the classification, as well as the “state of the art” of this topic, focuses on the link between CPP and cargo.
European Journal of Organic Chemistry, 2013
Here we present a new formulation of the recently introduced OxymaPure additive for peptide bond ... more Here we present a new formulation of the recently introduced OxymaPure additive for peptide bond formation, in which the N-hydroxylamine group is replaced by a potassium salt. The complete suppression of its acidity converts K-Oxyma into the most suitable coupling choice when peptides are assembled on highly acid-labile solid-supports. The cou-
Memórias do Instituto Oswaldo Cruz, 2002
Cytotoxicity assays of 24 new 3,5-disubstituted-tetrahydro-2H-1,3,5-thiadiazin-2-thione derivativ... more Cytotoxicity assays of 24 new 3,5-disubstituted-tetrahydro-2H-1,3,5-thiadiazin-2-thione derivatives were performed. The 17 compounds with higher anti-epimastigote activity and lower cytotoxicity were, thereafter, screened against amastigote of Trypanosoma cruzi. Out of these 17 derivatives S-2d was selected to be assayed in vivo, because of its remarkable trypanocidal properties. To determine toxicity against J774 macrophages, a method based on quantification of cell damage, after 24 h, was used. Cell respiration, an indicator of cell viability, was assessed by the reduction of MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] to formazan. Antiamastigote activity was estimated after 48 h by microscopic counts of May Grünwald-Giemsa-stained monolayers. Nifurtimox and benznidazole were used as reference drugs. For the in vivo experiences, mice were infected with 10 4 blood trypomastigotes and then treated during 15 days with S-2d or nifurtimox by oral route. All of the compounds were highly toxic at 100 µg/ml for macrophages and a few of them maintained this cytotoxicity even at 10 µg/ml. Of the derivatives assayed against amastigotes 3k and S-2d showed an interesting activity, that was held even at 1µg/ ml. It is demonstrated that the high anti-epimastigote activity previously reported is mainly due to the non-specific toxicity of these compounds. In vivo assays assessed a reduction of parasitemia after administration of S-2d to infected mice.
ACS combinatorial science, Jan 11, 2015
Click Chemistry is an approach that uses efficient and reliable reactions, such as Cu(I)-catalyze... more Click Chemistry is an approach that uses efficient and reliable reactions, such as Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC), mainly to bind two molecular building blocks. In addition, CuAAC has showed broad applications in medicinal chemistry and other fields of chemistry. The present review describes the general features and applications of CuAAC in solid-phase (CuAAC-SP), highlighting the suitability of this kind of reaction for peptides, nucleotides, small molecules, supramolecular structures, and polymers, among others. This versatile reaction is expected to become pivotal for meeting future challenges in solid-phase chemistry.
Organic Letters, 2013
A new resin for the solid-phase synthesis of peptide acids was developed. It was based on a linke... more A new resin for the solid-phase synthesis of peptide acids was developed. It was based on a linker with two unique features: methoxy groups as the only activating groups of the phenyl ring and a copper(I)-catalyzed Click chemistry reaction to anchor it to the solid support. The efficiency of this new resin in solid phase peptide synthesis was compared with that of Wang resin.
Peptides as drugs show unique characteristics (high biological activity, high specificity and low... more Peptides as drugs show unique characteristics (high biological activity, high specificity and low toxicity), thereby making them particularly attractive therapeutic agents. During the last years, the pharmaceutical industry, which was traditionally focused on small molecules, has been attracted by the benefits that peptides confer. This is due in part, for the great number of developments carried out in their synthetic strategies, mostly in the Solid-Phase mode.
ACS Combinatorial Science, 2013
An efficient, standard, mild, and copper-free imidazole-1-sulfonyl azide hydrochloride-based diaz... more An efficient, standard, mild, and copper-free imidazole-1-sulfonyl azide hydrochloride-based diazo-transfer method was implemented in a set of four resins that cover a broad range of hydrophobicity. The imidazole-1-sulfonyl azide hydrochloride is easily prepared/commercially available, stable upon storage at 4°C
Ultrasonics Sonochemistry, 2012
A facile, efficient and environment-friendly protocol for the synthesis of 6-chloro-5-formyl-1,4-... more A facile, efficient and environment-friendly protocol for the synthesis of 6-chloro-5-formyl-1,4-dihydropyridine derivatives has been developed by the convenient ultrasound-mediated reaction of 2(1H)pyridone derivatives with the Vilsmeier-Haack reagent. This method provides several advantages over current reaction methodologies including a simpler work-up procedure, shorter reaction times and higher yields.
QSAR & Combinatorial Science, 2006
An efficient solid-phase approach to prepare substituted 1,4,5,6-tetrahydro-6-oxopyridines bearin... more An efficient solid-phase approach to prepare substituted 1,4,5,6-tetrahydro-6-oxopyridines bearing a carboxylic acid group on C3 has been developed. The four-step protocol involves an initial acetoacetylation of polystyrene Wang resin, followed by preparation of resin-bound enamine. The cyclization reactions were carried out by reacting immobilized enamines with Knovenagel derivatives by a Hantzsch-type heterocyclization. Acidolytic cleavage from the solid support rendered the desired heterocyclic compounds in excellent yields and high purity. The synthesized compounds were structurally characterized by spectroscopic methods. In order to gain a better understanding of the structure of the obtained heterocycles, theoretical calculations at the ab initio (B3LYP/6-31G*) level were performed.
Journal of the Brazilian Chemical Society, 2011
Neste trabalho, realizou-se um estudo por ressonância magnética nuclear de 1 H, 13 C e 15 N de de... more Neste trabalho, realizou-se um estudo por ressonância magnética nuclear de 1 H, 13 C e 15 N de derivados de 1,4-dihidropiridinas que contêm, nos grupos ésteres das posições C-3 e C-5, longas cadeias alquílicas ou funcionalizadas. Atribuíram-se inequivocamente os sinais dos espectros utilizando experimentos 1D e 2D (DEPT, nOe, HMQC, HMBC, COSY).
European Journal of Organic Chemistry, 2000
Cyclopropanations between C 60 and readily available malonates bearing different steroid moieties... more Cyclopropanations between C 60 and readily available malonates bearing different steroid moieties (4-6) by the Bingel-Hirsch protocol has allowed the synthesis of a new series of hybrid functionalized chimeras (7-9). Whereas cycloadducts 7 and 8 showed the expected chemical structures, the presence of the diene moiety in the ergosterol unit of malonate 6 resulted in the production of the corresponding cycloadduct with an additional oxygen molecule. A thorough spectroscopical study ( 1 H and 13 C NMR, COSY, DEPT, Eur.
![Research paper thumbnail of Synthesis and antiprotozoan evaluation of new alkyl-linked bis(2-thioxo-[1,3,5]thiadiazinan-3-yl) carboxylic acids](https://attachments.academia-assets.com/44008994/thumbnails/1.jpg)
](Bioorganic & Medicinal Chemistry, 2005
Two new series of several alkyl-linked bis(2-thioxo-[1,3,5]thiadiazinan-3-yl) carboxylic acids we... more Two new series of several alkyl-linked bis(2-thioxo-[1,3,5]thiadiazinan-3-yl) carboxylic acids were synthesized in a two step procedure from the corresponding alkyl bis-dithiocarbamic salt intermediary. The novel compounds were evaluated for their activity in vitro against Trypanosoma cruzi strain CL (clone CL B5) and Trichomonas vaginalis strain JH 31A.
Here we present a new formulation of the recently introduced OxymaPure additive for peptide bond ... more Here we present a new formulation of the recently introduced OxymaPure additive for peptide bond formation, in which the N-hydroxylamine group is replaced by a potassium salt. The complete suppression of its acidity converts K-Oxyma into the most suitable coupling choice when peptides are assembled on highly acid-labile solid-supports. The cou
Tetrahydropyranyl (Thp), which exploits the concept of being an S,O-acetal nonaromatic protecting... more Tetrahydropyranyl (Thp), which exploits the concept of being an S,O-acetal nonaromatic protecting group for cysteine, has been shown to be superior to Trt, Dpm, Acm, and StBu in solid-phase peptide synthesis using the Fmoc/tBu strategy. Thus, Cys racemization and C-terminal 3-(1-piperidinyl)- alanine formation were minimized when the Cys was protected with Thp. This nonaromatic protecting group also improved the solubility of Cys-containing protected peptides.
Archiv der …, 2008
The synthesis and in-vitro antiprotozoal evaluation of novel N 4 -(benzyl)spermidyl-linked bis(1,... more The synthesis and in-vitro antiprotozoal evaluation of novel N 4 -(benzyl)spermidyl-linked bis(1,3,5thiadiazinane-2-thione) (bis-THTT) derivatives from N 4 -(benzyl)spermidine is disclosed. Several of the new bis-THTT have in-vitro activities against L. donovani and T. cruzi that are comparable or superior to those of currently employed protozoocidal agents.
Ultrasonics Sonochemistry, 2011
The condensation of Meldrum's acid, aromatic aldehydes, alkyl acetoacetates and ammonium acetate ... more The condensation of Meldrum's acid, aromatic aldehydes, alkyl acetoacetates and ammonium acetate in glacial acetic acid under ultrasound irradiation at room temperature results in the formation of 3,4-dihydropyridone derivatives (4a-p) in 85-96% yields. Compared with conventional methods, the main advantages of the present procedure are milder conditions, shorter reaction times and higher yields.
Beilstein Journal of Nanotechnology, 2014
Here we report on the self-organization characteristics in water of two diastereomer pairs of ful... more Here we report on the self-organization characteristics in water of two diastereomer pairs of fullerene-androsterone hybrids that have the hydrophobic C 60 appendage in the A and D ring of the androsterone moiety, respectively. The morphology and particle size in aqueous solution were determined by transmission electron microscopy (TEM) and dynamic light scattering (DLS), with satisfactory agreement between both techniques. In general, these fullerene derivatives are shown to organize into spherical nanoscale structures with diameters in the ranges of 10-20 and 30-50 nm, respectively.
Peptides 2015, Proceedings of the 24th American Peptide Symposium, 2015
The discovery and development of natural, synthetic or peptidomimetic cell-penetrating peptides (... more The discovery and development of natural, synthetic or peptidomimetic cell-penetrating peptides (CPPs) is a promising breakthrough to achieve non-invasive delivery of non-permeable biomolecules in the intracellular compartment. The CPPs are able to carry small molecules, plasmid DNA, interfering RNA, proteins, viruses, nanoparticles among others, across the cellular membrane, resulting in internalization of the intact cargos. In general, are sequence with 5-30 aminoacids, which are classified in cationics, amphipathics or hydrophobics, depending on its structural characteristics. The present review explores the classification, as well as the “state of the art” of this topic, focuses on the link between CPP and cargo.
European Journal of Organic Chemistry, 2013
Here we present a new formulation of the recently introduced OxymaPure additive for peptide bond ... more Here we present a new formulation of the recently introduced OxymaPure additive for peptide bond formation, in which the N-hydroxylamine group is replaced by a potassium salt. The complete suppression of its acidity converts K-Oxyma into the most suitable coupling choice when peptides are assembled on highly acid-labile solid-supports. The cou-
Memórias do Instituto Oswaldo Cruz, 2002
Cytotoxicity assays of 24 new 3,5-disubstituted-tetrahydro-2H-1,3,5-thiadiazin-2-thione derivativ... more Cytotoxicity assays of 24 new 3,5-disubstituted-tetrahydro-2H-1,3,5-thiadiazin-2-thione derivatives were performed. The 17 compounds with higher anti-epimastigote activity and lower cytotoxicity were, thereafter, screened against amastigote of Trypanosoma cruzi. Out of these 17 derivatives S-2d was selected to be assayed in vivo, because of its remarkable trypanocidal properties. To determine toxicity against J774 macrophages, a method based on quantification of cell damage, after 24 h, was used. Cell respiration, an indicator of cell viability, was assessed by the reduction of MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] to formazan. Antiamastigote activity was estimated after 48 h by microscopic counts of May Grünwald-Giemsa-stained monolayers. Nifurtimox and benznidazole were used as reference drugs. For the in vivo experiences, mice were infected with 10 4 blood trypomastigotes and then treated during 15 days with S-2d or nifurtimox by oral route. All of the compounds were highly toxic at 100 µg/ml for macrophages and a few of them maintained this cytotoxicity even at 10 µg/ml. Of the derivatives assayed against amastigotes 3k and S-2d showed an interesting activity, that was held even at 1µg/ ml. It is demonstrated that the high anti-epimastigote activity previously reported is mainly due to the non-specific toxicity of these compounds. In vivo assays assessed a reduction of parasitemia after administration of S-2d to infected mice.
ACS combinatorial science, Jan 11, 2015
Click Chemistry is an approach that uses efficient and reliable reactions, such as Cu(I)-catalyze... more Click Chemistry is an approach that uses efficient and reliable reactions, such as Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC), mainly to bind two molecular building blocks. In addition, CuAAC has showed broad applications in medicinal chemistry and other fields of chemistry. The present review describes the general features and applications of CuAAC in solid-phase (CuAAC-SP), highlighting the suitability of this kind of reaction for peptides, nucleotides, small molecules, supramolecular structures, and polymers, among others. This versatile reaction is expected to become pivotal for meeting future challenges in solid-phase chemistry.
Organic Letters, 2013
A new resin for the solid-phase synthesis of peptide acids was developed. It was based on a linke... more A new resin for the solid-phase synthesis of peptide acids was developed. It was based on a linker with two unique features: methoxy groups as the only activating groups of the phenyl ring and a copper(I)-catalyzed Click chemistry reaction to anchor it to the solid support. The efficiency of this new resin in solid phase peptide synthesis was compared with that of Wang resin.
Peptides as drugs show unique characteristics (high biological activity, high specificity and low... more Peptides as drugs show unique characteristics (high biological activity, high specificity and low toxicity), thereby making them particularly attractive therapeutic agents. During the last years, the pharmaceutical industry, which was traditionally focused on small molecules, has been attracted by the benefits that peptides confer. This is due in part, for the great number of developments carried out in their synthetic strategies, mostly in the Solid-Phase mode.
ACS Combinatorial Science, 2013
An efficient, standard, mild, and copper-free imidazole-1-sulfonyl azide hydrochloride-based diaz... more An efficient, standard, mild, and copper-free imidazole-1-sulfonyl azide hydrochloride-based diazo-transfer method was implemented in a set of four resins that cover a broad range of hydrophobicity. The imidazole-1-sulfonyl azide hydrochloride is easily prepared/commercially available, stable upon storage at 4°C
Ultrasonics Sonochemistry, 2012
A facile, efficient and environment-friendly protocol for the synthesis of 6-chloro-5-formyl-1,4-... more A facile, efficient and environment-friendly protocol for the synthesis of 6-chloro-5-formyl-1,4-dihydropyridine derivatives has been developed by the convenient ultrasound-mediated reaction of 2(1H)pyridone derivatives with the Vilsmeier-Haack reagent. This method provides several advantages over current reaction methodologies including a simpler work-up procedure, shorter reaction times and higher yields.
QSAR & Combinatorial Science, 2006
An efficient solid-phase approach to prepare substituted 1,4,5,6-tetrahydro-6-oxopyridines bearin... more An efficient solid-phase approach to prepare substituted 1,4,5,6-tetrahydro-6-oxopyridines bearing a carboxylic acid group on C3 has been developed. The four-step protocol involves an initial acetoacetylation of polystyrene Wang resin, followed by preparation of resin-bound enamine. The cyclization reactions were carried out by reacting immobilized enamines with Knovenagel derivatives by a Hantzsch-type heterocyclization. Acidolytic cleavage from the solid support rendered the desired heterocyclic compounds in excellent yields and high purity. The synthesized compounds were structurally characterized by spectroscopic methods. In order to gain a better understanding of the structure of the obtained heterocycles, theoretical calculations at the ab initio (B3LYP/6-31G*) level were performed.
Journal of the Brazilian Chemical Society, 2011
Neste trabalho, realizou-se um estudo por ressonância magnética nuclear de 1 H, 13 C e 15 N de de... more Neste trabalho, realizou-se um estudo por ressonância magnética nuclear de 1 H, 13 C e 15 N de derivados de 1,4-dihidropiridinas que contêm, nos grupos ésteres das posições C-3 e C-5, longas cadeias alquílicas ou funcionalizadas. Atribuíram-se inequivocamente os sinais dos espectros utilizando experimentos 1D e 2D (DEPT, nOe, HMQC, HMBC, COSY).
European Journal of Organic Chemistry, 2000
Cyclopropanations between C 60 and readily available malonates bearing different steroid moieties... more Cyclopropanations between C 60 and readily available malonates bearing different steroid moieties (4-6) by the Bingel-Hirsch protocol has allowed the synthesis of a new series of hybrid functionalized chimeras (7-9). Whereas cycloadducts 7 and 8 showed the expected chemical structures, the presence of the diene moiety in the ergosterol unit of malonate 6 resulted in the production of the corresponding cycloadduct with an additional oxygen molecule. A thorough spectroscopical study ( 1 H and 13 C NMR, COSY, DEPT, Eur.
Bioorganic & Medicinal Chemistry, 2005
Two new series of several alkyl-linked bis(2-thioxo-[1,3,5]thiadiazinan-3-yl) carboxylic acids we... more Two new series of several alkyl-linked bis(2-thioxo-[1,3,5]thiadiazinan-3-yl) carboxylic acids were synthesized in a two step procedure from the corresponding alkyl bis-dithiocarbamic salt intermediary. The novel compounds were evaluated for their activity in vitro against Trypanosoma cruzi strain CL (clone CL B5) and Trichomonas vaginalis strain JH 31A.
Here we present a new formulation of the recently introduced OxymaPure additive for peptide bond ... more Here we present a new formulation of the recently introduced OxymaPure additive for peptide bond formation, in which the N-hydroxylamine group is replaced by a potassium salt. The complete suppression of its acidity converts K-Oxyma into the most suitable coupling choice when peptides are assembled on highly acid-labile solid-supports. The cou
Tetrahydropyranyl (Thp), which exploits the concept of being an S,O-acetal nonaromatic protecting... more Tetrahydropyranyl (Thp), which exploits the concept of being an S,O-acetal nonaromatic protecting group for cysteine, has been shown to be superior to Trt, Dpm, Acm, and StBu in solid-phase peptide synthesis using the Fmoc/tBu strategy. Thus, Cys racemization and C-terminal 3-(1-piperidinyl)- alanine formation were minimized when the Cys was protected with Thp. This nonaromatic protecting group also improved the solubility of Cys-containing protected peptides.
Archiv der …, 2008
The synthesis and in-vitro antiprotozoal evaluation of novel N 4 -(benzyl)spermidyl-linked bis(1,... more The synthesis and in-vitro antiprotozoal evaluation of novel N 4 -(benzyl)spermidyl-linked bis(1,3,5thiadiazinane-2-thione) (bis-THTT) derivatives from N 4 -(benzyl)spermidine is disclosed. Several of the new bis-THTT have in-vitro activities against L. donovani and T. cruzi that are comparable or superior to those of currently employed protozoocidal agents.
Ultrasonics Sonochemistry, 2011
The condensation of Meldrum's acid, aromatic aldehydes, alkyl acetoacetates and ammonium acetate ... more The condensation of Meldrum's acid, aromatic aldehydes, alkyl acetoacetates and ammonium acetate in glacial acetic acid under ultrasound irradiation at room temperature results in the formation of 3,4-dihydropyridone derivatives (4a-p) in 85-96% yields. Compared with conventional methods, the main advantages of the present procedure are milder conditions, shorter reaction times and higher yields.
Beilstein Journal of Nanotechnology, 2014
Here we report on the self-organization characteristics in water of two diastereomer pairs of ful... more Here we report on the self-organization characteristics in water of two diastereomer pairs of fullerene-androsterone hybrids that have the hydrophobic C 60 appendage in the A and D ring of the androsterone moiety, respectively. The morphology and particle size in aqueous solution were determined by transmission electron microscopy (TEM) and dynamic light scattering (DLS), with satisfactory agreement between both techniques. In general, these fullerene derivatives are shown to organize into spherical nanoscale structures with diameters in the ranges of 10-20 and 30-50 nm, respectively.