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1.
Chem Biodivers ; : e202401315, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39136528

ABSTRACT

We have synthesized a series of novel coumarin-steroid and triterpenoid hybrids and evaluated their potential anticancer activity through molecular docking calculations and in vitro antiproliferative assays. These hybrids, derived from estrone and oleanolic acid, were linked via hydrocarbon spacers of varying lengths. Molecular docking studies against human aromatase revealed strong interactions, particularly for compound 11d, which exhibited significant binding affinity (-12.6308 kcal/mol). In vitro assays demonstrated that compounds 6b and 11d had notable antiproliferative effects, with GI50 values of 5.4 and 7.0 µM against WiDr (colon) and HeLa (cervix) cancer cells, respectively. These findings highlight the potential of these hybrids as novel anticancer agents targeting aromatase, warranting further investigation and optimization.

2.
Inorg Chem ; 63(15): 6649-6659, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38572737

ABSTRACT

Novel four-coordinated boron complexes (1-5) were synthesized via a reaction between BF3·CH3OH and benzimidazole-phenolate ligands (L1-L5), which are N,O-donors. These complexes exhibit intense blue emission in the solution and solid states accompanied by notable fluorescence quantum yields (ΦF). The study of the structure-property relation, through theoretical and experimental approaches, revealed a distinctive trend where compounds incorporating electron-donating substituents (methyl and ethoxy groups) in the phenolate moiety manifest shifts in emission wavelengths across the blue spectrum, concomitant with an increase in ΦF. Furthermore, the incorporation of an aromatic ring into the benzimidazole moiety considerably intensifies the rate of radiative relaxation from excited states. Notably, in the solid phase, either as a crystalline powder or loaded into polymer films, these modified complexes maintain or even surpass ΦF values observed in molecular solutions, ranging from 0.18 to 0.57, depending on the substitution. This characteristic makes these compounds attractive for applications in optoelectronics. All of the compounds were characterized using 1H, 13C, 11B, and 19F NMR, elemental analysis, and the molecular structures were corroborated through single-crystal X-ray diffraction analysis. Computational calculations via time-dependent density functional theory further elucidate the tunability of optical bandgaps through group substitution on ligands, aligning well with experimental observations.

3.
Steroids ; 192: 109173, 2023 04.
Article in English | MEDLINE | ID: mdl-36621620

ABSTRACT

Estrogens play a pivotal role in the development of estrogen-dependent breast cancer and other hormone-dependent disorders. A common strategy to overcome the pathological effects of estrogens is the use of aromatase inhibitors (AIs), which bind to the enzyme and prevent the union with the natural substrate, decreasing the amount of estrogens produced. Several AIs have been developed, including inhibitors with a steroidal backbone and a nitrogen heterocycle in their structure. Encouraged by the notable results presented by current and clinical steroidal drugs, herein we present the synthesis of a steroidal spiro morpholinone derivative as a plausible aromatase inhibitor. The morpholinone derivative was synthesized over a six-step methodology starting from estrone. The title compound and its hydroxychloroacetamide derivative precursor were evaluated for their antiproliferative profile against estrogen-dependent and independent solid tumor cell lines: A549, HBL-100, HeLa, SW1573, T-47D and WiDr. Both compounds exhibited a potent antiproliferative activity in the micromolar range against the six cancer cell lines, with the hydroxychloroacetamide derivative precursor being a more potent inhibitor (GI50 = 0.25-2.4 µM) than the morpholinone derivative (GI50 = 2.0-11 µM). Furthermore, both compounds showed, in almost all cases, better GI50 values than the steroidal anticancer drugs abiraterone and galeterone. Docking simulations of the derivatives were performed in order to explain the experimental biological activity. The results showed interactions with the iron heme (derivative 3) and important residues of the steroidal binding-site (Met374) for the inhibition of human aromatase. A correlation was found between in vitro assays and the score obtained from the molecular docking study.


Subject(s)
Antineoplastic Agents , Breast Neoplasms , Female , Humans , Antineoplastic Agents/chemistry , Aromatase Inhibitors/chemistry , Breast Neoplasms/metabolism , Cell Line, Tumor , Cell Proliferation , Estrogens/pharmacology , Estrone/pharmacology , Molecular Docking Simulation , Molecular Structure , Structure-Activity Relationship , Morpholines/chemical synthesis , Morpholines/pharmacology
4.
Rev. cuba. cir ; 61(1)mar. 2022.
Article in Spanish | LILACS, CUMED | ID: biblio-1408235

ABSTRACT

Introducción: La fístula traqueocutánea es la complicación más frecuente de la traqueostomía, que lleva a la necesidad de usar diferentes tipos de plastias para lograr un cierre definitivo. Objetivo: Mostrar una opción de tratamiento quirúrgico para garantizar un cierre definitivo de la fístula traqueocutánea recidivante. Caso clínico: Se presenta paciente masculino de 45 años con antecedentes de traqueostomía sin cierre espontáneo; quien desarrolló fístula traqueocutánea tratada con doble plastia de deslizamiento frontal tipo Szymanowski, con posterior recidiva, motivo por el que acude a consulta. Se realizó cierre directo de mucosa traqueal con plicatura de músculo platisma y avance de colgajos de piel rectangulares para reforzar cobertura de la pared anterior de la tráquea. Se logró corregir la fístula mediante un procedimiento simple, rápido y efectivo. Conclusiones: Este método evita las dificultades encontradas en otros procedimientos y garantiza la corrección funcional y estética con el empleo de una técnica simple con baja morbilidad(AU)


Introduction: Tracheocutaneous fistula is the most frequent complication of tracheostomy, leading to the need to use different types of plasties to achieve a definitive closure. Objective: To show a surgical treatment option for guaranteeing a definitive closure of recurrent tracheocutaneous fistula. Clinical case: We present the case of a 45-year-old male patient with a history of tracheostomy without spontaneous closure, who developed tracheocutaneous fistula managed through double plasty of anterior sliding of Szymanowski type, followed by recurrence. Direct closure of the tracheal mucosa was performed with platysma muscle plication and advancement of rectangular skin flaps for reinforcing coverage of the anterior wall of the trachea. Correction of the fistula was achieved by a simple, fast and effective procedure. Conclusions: This method avoids the difficulties found in other procedures, and guarantees functional and aesthetic correction with the use of a simple technique with low morbidity(AU)


Subject(s)
Humans , Male , Adult , Tracheostomy/adverse effects , Esthetics , Fistula
5.
Materials (Basel) ; 14(18)2021 Sep 19.
Article in English | MEDLINE | ID: mdl-34576654

ABSTRACT

The present study focuses on an introductory analysis of the use of three xanthophylls as additives for green lubricant applications. For this purpose, the additives were characterized by FTIR and 1H-NMR techniques, and the bio-lubricants were described by their physical properties. The effect of the natural compounds on the friction and wear properties of bio-lubricants were evaluated by sliding friction tests under boundary conditions, as confirmed by an analysis of the lubricating film thickness. The antioxidant capacity was analyzed by FTIR spectroscopy. It was observed better wear protection in castor oil with xanthophylls than without these additives. The wear rate was reduced up to 50% compared with neat oil. Lesser beneficial effects were appreciated in friction coefficient since it was increased 25%. The best contribution was observed with astaxanthin as an additive. In addition, a significant improvement in the oxidation of castor oil, complemented with this additive, was exhibited by FTIR analysis. It was found that xanthophylls could be employed as additives for totally biodegradable lubricant applications since they have better tribological and antioxidant behavior than current additives.

6.
Rev. cuba. cir ; 59(3): e976, jul.-set. 2020. tab
Article in Spanish | LILACS, CUMED | ID: biblio-1144433

ABSTRACT

RESUMEN Introducción: Las úlceras por presión son soluciones de continuidad que aparecen en la piel que cubre las prominencias óseas, cuando estas soportan una presión externa continuada que interfiere con la circulación sanguínea correcta y la nutrición de los tejidos. Objetiv o: Evaluar los resultados del tratamiento quirúrgico de las úlceras por presión mediante los diferentes tipos de colgajos locales. Métodos: Se realizó un estudio descriptivo, ambispectivo y de corte longitudinal. El universo estuvo conformado por todos los pacientes que presentaron diagnóstico de úlcera por presión con criterio quirúrgico. La muestra fueron 72 pacientes constituyendo un total de 84 úlceras por presión, que cumplieron con los criterios de inclusión. Resultados: El sexo masculino predominó en el estudio; con rango de edad entre 19 y 29 años. Las úlceras sacras fueron las más frecuentes y de mayor tamaño y el colgajo más utilizado para el cierre fue el de rotación y avance. Se obtuvo un resultado satisfactorio en el 82,5 por ciento de los casos. Conclusiones: Se logró una adecuada cobertura tisular y almohadillado de la zona, además de ausencia de complicaciones que interfirieran con el resultado final(AU)


ABSTRACT Introduction: Pressure ulcers are continuity solutions that appear on the skin that covers bony prominences, when these bear continuous external pressure that interferes with correct blood circulation and nutrition of tissues. Objective: To evaluate the outcomes of surgical treatment of pressure ulcers using different types of local flaps. Methods: A descriptive, ambispective and longitudinal study was carried out. The population consisted of all the patients who presented diagnosis of pressure ulcer with surgical criteria. The sample consisted of 72 patients, with a total of 84 pressure ulcers, who met the inclusion criteria. Results: The male sex predominated in the study, together with the age range 19-29 years. Sacral ulcers were the most frequent and largest, and the most used flap for closure was the rotation and advancement flap. Satisfactory outcomes were obtained in 82.5 percent of the cases. Conclusions: Adequate tissue coverage and padding of the area was achieved, as well as the absence of complications that interfered with the final outcomes(AU)


Subject(s)
Humans , Male , Young Adult , Surgical Flaps/adverse effects , Pressure Ulcer/surgery , Pressure Ulcer/diagnosis , Epidemiology, Descriptive , Longitudinal Studies
7.
Molecules ; 24(20)2019 Oct 12.
Article in English | MEDLINE | ID: mdl-31614780

ABSTRACT

A small and focused library of steroidal non-fused and fused pyrimidines was prepared from pregnenolone acetate and diosgenin, respectively. The key step was the cycloaddition reaction of nitrogen-containing 1,3-binucleophiles with the steroidal α,ß-unsaturated ketone. Urea, thiourea and guanidine reacted in a similar manner and afforded the steroidal pyrimidines in good yields. The antiproliferative tests against human tumor cell lines gave GI50 values in the micromolar range and had no effect on healthy fibroblasts. Additional experiments indicated that the compounds did not act as P-glycoprotein substrates, thus avoiding the rise of drug resistance. The fused steroidal pyrimidinethione was selected as drug lead for further testing due to its strong antiproliferative activities within the low micromolar range.


Subject(s)
Cell Proliferation/drug effects , Neoplasms/drug therapy , Pyrimidines/pharmacology , Steroids/pharmacology , Acetates/chemistry , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans , Nitrogen/chemistry , Pregnenolone/chemistry , Pyrimidines/chemical synthesis , Pyrimidines/chemistry , Steroids/chemical synthesis , Steroids/chemistry , Structure-Activity Relationship
8.
Mem Inst Oswaldo Cruz ; 114: e180569, 2019.
Article in English | MEDLINE | ID: mdl-31166479

ABSTRACT

BACKGROUND: Currently, there is an increasing global interest for the study of how infectious diseases could be linked to climate and weather variability. The Chagas disease was described in 1909 by Carlos Chagas, and is caused by the flagellate protozoan Trypanosoma cruzi. The Chagas disease is considered one of the biggest concerns in public health in Latin America. In Chile, the main vectors involved in the transmission of T. cruzi are arthropods of the Triatominae subfamily. Moreover, another main transmission way is through of vectors by fecal-urine way, however, oral way also has been described among others transmission form. OBJECTIVES: In order to get understand outbreaks of Chagas-disease, we search for possible relationships between the frequency of cases in the Chilean population and atmospheric oscillations. METHODS: We explored the two most important atmospheric oscillations in the Southern Hemisphere: southern oscillation index (SOI) and Antarctic oscillation (AAO), during the available years with official data. Because the number of migrant people born outside from Chile increasing significantively between 2014 and 2018, we used for the analysis two different periods from data available official data: (i) 2001 to 2014, (ii) 2001 to 2017. FINDINGS: For both periods we observed a significant and positive relation between AAO one year before. However, for the 2001 to 2014 period positive SOI one year before, which is related with La Niña phases, was the more important variable. MAIN CONCLUSIONS: The Chagas disease frequency per year in Chile was found to depend mainly on SOI in previous year, whose values can be determined one year in advance. Therefore, it is possible to partially forecast annual frequency patterns. This could have important applications in public health strategies and for allocating resources for the management of the disease.


Subject(s)
Atmosphere , Chagas Disease/epidemiology , Climate Change , Disease Outbreaks/statistics & numerical data , Chagas Disease/transmission , Chile/epidemiology , Humans , Reference Values , Time Factors
9.
Molecules ; 24(7)2019 Apr 09.
Article in English | MEDLINE | ID: mdl-30970551

ABSTRACT

Carotenoids are natural compounds that have important roles in promoting and maintaining human health. Synthetic astaxanthin is a highly requested product by the aquaculture industry, but natural astaxanthin is not. Various strategies have been developed to synthesize this carotenoid. Nonetheless, these approaches have not only provided limited global yields, but its main commercial source also carries several health risks for humans. In this contribution, the one-pot base-catalyzed reaction of (3R,3'R,6'R)-lutein (1) esters has resulted in a successful isomerization process to easily obtain up to 95% meso-zeaxanthin (2), which in turn is oxidized to (3R,3'S)-astaxanthin (3) with a global yield of 68%. The same oxidation performed with UV irradiation (365 nm) for 5 min provided the highest global yield (76%). These chemical transformations have also been achieved with a significant reduction of the health risks associated with its potential human consumption. Furthermore, this is the first time only one of the configurational isomers has been obtained semisynthetically. The poorly understood formation mechanisms of these two compounds were also investigated using Density-Functional Theory (DFT) calculations. These theoretical studies revealed that the isomerization involves a base-catalyzed deprotonation at C-6', followed by C-4' protonation, while the oxidation occurs via free radical mechanisms.


Subject(s)
Lutein , Models, Chemical , Humans , Lutein/chemical synthesis , Lutein/chemistry , Molecular Structure , Stereoisomerism , Xanthophylls/chemical synthesis , Xanthophylls/chemistry , Zeaxanthins/chemical synthesis , Zeaxanthins/chemistry
10.
Mem. Inst. Oswaldo Cruz ; 114: e180569, 2019. tab, graf
Article in English | LILACS | ID: biblio-1012668

ABSTRACT

BACKGROUND Currently, there is an increasing global interest for the study of how infectious diseases could be linked to climate and weather variability. The Chagas disease was described in 1909 by Carlos Chagas, and is caused by the flagellate protozoan Trypanosoma cruzi. The Chagas disease is considered one of the biggest concerns in public health in Latin America. In Chile, the main vectors involved in the transmission of T. cruzi are arthropods of the Triatominae subfamily. Moreover, another main transmission way is through of vectors by fecal-urine way, however, oral way also has been described among others transmission form. OBJECTIVES In order to get understand outbreaks of Chagas-disease, we search for possible relationships between the frequency of cases in the Chilean population and atmospheric oscillations. METHODS We explored the two most important atmospheric oscillations in the Southern Hemisphere: southern oscillation index (SOI) and Antarctic oscillation (AAO), during the available years with official data. Because the number of migrant people born outside from Chile increasing significantively between 2014 and 2018, we used for the analysis two different periods from data available official data: (i) 2001 to 2014, (ii) 2001 to 2017. FINDINGS For both periods we observed a significant and positive relation between AAO one year before. However, for the 2001 to 2014 period positive SOI one year before, which is related with La Niña phases, was the more important variable. MAIN CONCLUSIONS The Chagas disease frequency per year in Chile was found to depend mainly on SOI in previous year, whose values can be determined one year in advance. Therefore, it is possible to partially forecast annual frequency patterns. This could have important applications in public health strategies and for allocating resources for the management of the disease.


Subject(s)
Humans , Communicable Diseases , Chagas Disease/diagnosis , Chile/epidemiology
11.
Eur J Med Chem ; 143: 21-32, 2018 Jan 01.
Article in English | MEDLINE | ID: mdl-29172080

ABSTRACT

Herein we report the straightforward preparation of novel conformationally-restricted steroids from trans-androsterone and estrone, decorated with spiranic oxazolidin-2-one or 2-aminooxazoline motifs at C-17 as potential antiproliferative agents. Such unprecedented pharmacophores were accessed using an aminomethylalcohol derivative at C-17 as the key intermediate; reaction of such functionality with triphosgene, or conversion into N-substituted thioureas, followed by an intramolecular cyclodesulfurization reaction promoted by yellow HgO, furnished such spirocycles in excellent yields. Title compounds were tested in vitro against a panel of six human tumor cell lines, named A549 (non-small cell lung), HBL-100 (breast), HeLa (cervix), SW1573 (non-small cell lung), T-47D (breast) and WiDr (colon), and the results were compared with steroidal chemotherapeutic agents (abiraterone and galeterone); the A-ring of the steroidal backbone, the nature of the heterocycle and the N-substituents proved to be essential motifs for establishing structure-activity relationships concerning not only the potency but also the selectivity against tumor cell lines. Estrone derivatives, particularly those bearing a spiranic 2-aminooxazoline scaffold were found to be the most active compounds, with GI50 values ranging from the low micromolar to the submicromolar level (0.34-1.5 µM). Noteworthy, the lead compounds showed a remarkable increase in activity against the resistant cancer cell lines (T-47D and WiDr) compared to the anticancer reference drugs (up to 120-fold).


Subject(s)
Antineoplastic Agents/pharmacology , Heterocyclic Compounds/pharmacology , Spiro Compounds/pharmacology , Steroids/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Crystallography, X-Ray , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Heterocyclic Compounds/chemical synthesis , Heterocyclic Compounds/chemistry , Humans , Models, Molecular , Molecular Structure , Spiro Compounds/chemical synthesis , Spiro Compounds/chemistry , Steroids/chemical synthesis , Steroids/chemistry , Structure-Activity Relationship
12.
Org Biomol Chem ; 15(23): 5041-5054, 2017 Jun 14.
Article in English | MEDLINE | ID: mdl-28574071

ABSTRACT

Starting from natural steroids (diosgenin, hecogenin, smilagenin, estrone), we have prepared a wide panel of selenoderivatives, including benzoselenazolones, selenosemicarbazones, isoselenocyanates, selenoureas, selenocyanates and diselenides, with the aim of developing new families of potential chemotherapeutic agents. The modification of the organoselenium moieties, and their position on the steroid provided valuable information concerning the antiproliferative activities. Among all the families accessed herein, the best profile was achieved for selenoureas on the A ring of estrone, which exhibited GI50 values in the range 2.0-4.1 µM for all the tested tumor cell lines, with increased potency compared with commonly used chemotherapeutic agents, like 5-fluorouracil and cisplatin. Cell cycle analysis revealed that selenoureas induced accumulation of cells in the G1 phase of the cell cycle in the breast cancer cell lines HBL-100 and T-47D; therefore, a different mechanism than cisplatin, that induces cell cycle accumulation in the S phase as a result of DNA damage, must be involved. In the rest of the tumor cells, a slight increase of the S compartment was observed. Moreover, selenosteoids turned out to be excellent glutathione peroxidase (GPx) mimics for the catalytic removal of deleterious H2O2 (t1/2 8.0-22.5 min) and alkyl peroxides (t1/2 23.0-38.9 min) when used in substoichiometric amounts (1% molar ratio), thus providing a valuable tool for reducing the intrinsic oxidative stress in tumor progression.


Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Free Radical Scavengers/chemistry , Free Radical Scavengers/pharmacology , Organoselenium Compounds/chemistry , Organoselenium Compounds/pharmacology , Steroids/chemistry , Biphenyl Compounds/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Humans , Hydrogen Peroxide/chemistry , Picrates/chemistry
13.
Steroids ; 122: 24-33, 2017 06.
Article in English | MEDLINE | ID: mdl-28396219

ABSTRACT

A novel three-step methodology to obtain 6a-aza-B-homo steroidal lactams has been developed starting from the easily available cholesterol and pregnenolone. In addition, a new procedure for the synthesis of a 6a-aza-B-homo steroidal lactam analog of vespertilin, starting from diosgenin has been established. In both synthetic pathways, the key intermediate is a hydroxyimino derivative obtained in a one- or two-step sequence from the starting materials. These methods avoid the use of hazardous oxidant agents in the process. The new steroidal oximes and lactams were examined for their antiproliferative activities against several tumor cell lines. The 6,23-dihydroxyimino derivative exhibited the highest activity with GI50 values of 11-22µM.


Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Lactams/chemistry , Oximes/chemistry , Steroids/chemical synthesis , Steroids/pharmacology , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Chemistry Techniques, Synthetic , Humans , Models, Molecular , Molecular Conformation , Steroids/chemistry
14.
Steroids ; 116: 13-19, 2016 12.
Article in English | MEDLINE | ID: mdl-27692994

ABSTRACT

The synthesis of several monomeric and dimeric steroidal [1,2,4]triazolo[1,5-a]pyrimidines (TPs) derived from steroids are described. These derivatives were prepared from α,ß-unsaturated carbonyl compounds through a Claisen Schmidt condensation and rearrangement of the spiro moiety followed by a cycloaddition with 3-amino-1,2,4-triazole. The antiproliferative activity of compounds 7, 13-15 was tested against human cancer cells; several IG50 values were below 10µM.


Subject(s)
Pyrimidines/chemistry , Steroids/chemical synthesis , Triazoles/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Humans , Stereoisomerism , Steroids/chemistry , Steroids/pharmacology
15.
Eur J Med Chem ; 99: 67-81, 2015 Jun 24.
Article in English | MEDLINE | ID: mdl-26046314

ABSTRACT

The stereoselective preparation of diosgenin-derived thio(seleno)ureas and glycomimetics bearing a 1,2,3-triazolyl tether on C-3 has been accomplished. The key steps in the synthetic pathway are the incorporation of an amino moiety and its further transformation into thio- and selenoureas, and also a click chemistry reaction involving a propargyl residue and an azido moiety to afford carbohydrate-derived 1,2,3-triazoles; subsequent BF3-promoted acetolysis of the spiranic moiety afforded the corresponding 22-oxocholestanic structure. The N-phenyl selenourea, an hitherto unknown steroidal derivative, turned out to be a potent ROS scavenger, in particular against free radicals (EC50 = 29.47 ± 2.33 µM, DPPH method), and as a glutathione peroxidase mimic in the elimination of H2O2 (t1/2 = 4.8 min, 1% molar ratio). 22-Oxocholestane structures bearing a C-3 azido, propargyl, thioureido, and particularly selenoureido moiety behaved as strong antiproliferative agents against HeLa cells (IC50 1.87-11.80 µM). N-phenyl selenourea also exhibited IC50 values lower than 6.50 µM for MDA-MB-231, MCF-7 and HepG2 cancer cells; apoptosis was found to be involved in its mode of action. Such compound was also capable of efficiently eliminating ROS endogenously produced by HeLa cells. Antiproliferative properties of thioxo and selenoxo derivatives were stronger than diosgenin.


Subject(s)
Diosgenin/chemistry , Diosgenin/pharmacology , Drug Design , Glycoconjugates/chemistry , Glycoconjugates/pharmacology , Organoselenium Compounds/chemistry , Triazoles/chemistry , Urea/analogs & derivatives , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/metabolism , Antineoplastic Agents/pharmacology , Biomimetic Materials/chemistry , Biomimetic Materials/metabolism , Biomimetic Materials/pharmacology , Biphenyl Compounds/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Diosgenin/metabolism , Drug Screening Assays, Antitumor , Free Radical Scavengers/chemistry , Free Radical Scavengers/pharmacology , Glutathione Peroxidase/metabolism , Glycoconjugates/metabolism , Humans , Mice , Picrates/metabolism , Reactive Oxygen Species/metabolism , Urea/chemistry
16.
Steroids ; 87: 86-92, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24928724

ABSTRACT

An efficient and facile synthesis of fused, substituted and spiro pyrazoline steroid derivatives through a cycloaddition reaction of different α,ß-unsaturated ketones with hydrazine acetate in acetic acid is reported. Depending on the starting material, the ring closure reaction provided a mixture of two steroidal pyrazoline epimers that were separated and studied by NMR techniques. In one case it was possible to isolate and characterize the hydrazone derivative as the reaction intermediate, which confirms the mechanism proposed in the literature [11,25,26].


Subject(s)
Pyrazoles/chemistry , Spiro Compounds/chemistry , Steroids/chemistry , Steroids/chemical synthesis , Chemistry Techniques, Synthetic , Hydrazines/chemistry
17.
Steroids ; 78(9): 902-8, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23643845

ABSTRACT

Recognizing the functionality of the pentacyclic steroidal derivative 7a as important synthon to obtain new brassinosteroid analogs, we have accomplished the derivatization of hecogenin, a sapogenin from the 25R serie containing a carbonyl group at C-12, to a 22,23-dioxocholestanic chain derivative. Starting from hecogenin acetate (5a) or hecogenin tosylate (5b), we obtained two pentacyclic derivatives (7a and 7b) which were subjected to an oxidation reaction on the double bond at C-12(23) to obtain a 22,23-dioxocholestanic chain, with the regeneration of the carbonyl group at C-12. Reduction of the carbonyl groups lead to the 20-epi-12,23-dihydroxy-22-oxo system 11a-b. The absolute configuration of compound 11a was established by X-ray diffraction analysis.


Subject(s)
Brassinosteroids/chemical synthesis , Brassinosteroids/chemistry , Crystallography, X-Ray , Hydroxylation , Models, Molecular , Molecular Conformation , Oxidation-Reduction , Spiro Compounds/chemistry , Steroids/chemistry
18.
Rev. cuba. med ; 51(4): 336-343, oct.-dic. 2012.
Article in Spanish | LILACS | ID: lil-662296

ABSTRACT

La feohifomicosis es una entidad poco frecuente causada por hongos formadores de hifas de la familia Dematiaceae, afecta principalmente a pacientes inmunosuprimidos, produce lesiones subcutáneas en forma de quistes y pseudoquistes que en su mayoría se tratan con la exéresis quirúrgica y tratamiento medicamentoso con anfotericin B e itraconazol. Se describió un caso de feohifomicosis, en un paciente masculino de 38 años de edad, con antecedentes de enfermedad renal crónica, hepatitis por virus C adquirida en hemodiálisis. Recibe trasplante renal en el 2010 y se le aplica triple terapia inmunosupresora, tacrolimus, micofenolato mofetil y prednisona. Desarrolla diabetes mellitus postrasplante. Un año después del injerto, comienza a presentar lesiones dermatológicas pseudoquísticas violáceas, solitarias, que forman conglomerados, en la pantorrilla, el tobillo y los dedos de ambos pies. Mediante examen clínico, micológico y por biopsia de la lesión se diagnostica feohifomicosis. Se realizó tratamiento quirúrgico con exéresis de las lesiones y medicamentoso con itraconazol 200 mg al día, se modificó el tratamiento inmunosupresor según interacción del itraconazol con los anticalcineurínicos, se sustituyó este por everolimus. Tres meses después se observó evolución satisfactoria


Pheohyphomycosis is a rare disease caused by Dematiaceae family hypha-forming fungi; it mainly affects immunosuppresed patients and causes subcutaneous lesions in the form of cysts and pseudocysts that are mostly treated with surgery and amphotericin B and Itraconazol-based treatment. A case of pheohyphomycosis was presented in a 38 years-old man with a history of chronic renal disease and of hepatitis C caught in hemodialysis. He was a renal transplant recipient in 2010 and was administered a triple immunosuppressive treatment with tacrolimus, mycophenolate mophetil and prednisone. He developed post-transplant diabetes mellitus and one year after the transplantation, he presented with purplish blue-colored pseudocystic dermatological lesions forming clusters in his calves, ankles and toes. The clinical, mycological and biopsy exams of the lesions yielded the diagnosis of pheohyphomycosis. The lesions were surgically removed and then 200mg of itraconazol was administered daily. This treatment was changed on account of the interaction between itraconazol and the anti-calcineuric drugs. The patient was then prescribed everolimus. Three months later, the patient recovered satisfactorily


Subject(s)
Humans , Male , Young Adult , Phaeohyphomycosis/surgery , Phaeohyphomycosis/diagnosis , Phaeohyphomycosis/drug therapy , Itraconazole/therapeutic use , Kidney Transplantation/adverse effects , Kidney Transplantation/immunology
19.
Rev. medica electron ; 34(3): 334-343, mayo-jun. 2012.
Article in Spanish | LILACS | ID: lil-644756

ABSTRACT

El río Yumurí es uno de los tres ríos más importantes de la ciudad de Matanzas. De menos longitud y caudal que los otros dos, el río separa los barrios de Versalles y Matanzas, sin embargo, la belleza natural del paisaje se ve empañada por las condiciones higiénico-ambientales de sus márgenes y el vertimiento de residuales, a lo largo de su cauce, desde su nacimiento a la desembocadura. Tiene múltiples fuentes contaminantes, debido a la acción del hombre, y los asentamientos humanos; por lo que la investigación objeto de este trabajo es de tipo descriptiva, enmarcada en un período de tiempo comprendido entre septiembre de 1998 y diciembre de 2009. Se hizo un estudio de los parámetros físico-químicos y bacteriológicos que puedan estar afectados para la utilización de sus aguas para uso recreativo y pesquero en 4 sitios de muestreo a lo largo de su cauce. Se encontró que los resultados obtenidos del número más probable de coliformes totales y el número más probable de coliformes fecales invalidan al río a todo lo largo de su corriente para ser utilizado con fines recreativos como contacto directo e indirecto. Respecto a la utilización para uso pesquero, los valores más negativos físico-químicos se reportaron el 25 por ciento en el puente Watkins y el 19 por ciento en el puente peatonal. Los valores medios de nitrógeno amoniacal también presentaron una calidad dudosa para la pesca en estos dos sitios de muestreo.


The Yumuri river is one of the three most important rivers of Matanzas. Shorter and with less flow than the other two, the river divides the quarters of Versalles and Matanzas , but the natural beauty of the scenery is blurred by the hygienic-environmental status of its sides and the residues dumping alongside it, from its source to its mouth. It has many polluting sources, due to the people´s action, and the human settlements; so the research done is a descriptive one, during the period from September 1998 to December 2009. We studied the physic-chemical parameters that may have a negative effect on the recreational and fishing usage of its waters in four sampling places alongside the river bed. The obtained results showed that the most probable number of total coliforms and the most probable number of fecal coliforms invalidate the usage of the river all along its course with a recreational objective, for direct or indirect contact. Respecting the fishing usage, the most negative physic-chemical values were reported at the Watkins Bridge, 25 per cent, and at the pedestrian bridge, 19 per cent. The media values of the ammoniacal nitrogen also had a doubtful quality for fishing in these two sampling places.


Subject(s)
Water Quality , Environmental Pollution , River Pollution/analysis , Epidemiology, Descriptive
20.
Acta Crystallogr Sect E Struct Rep Online ; 68(Pt 12): o3331, 2012 Dec 01.
Article in English | MEDLINE | ID: mdl-23476170

ABSTRACT

THE STRUCTURE OF THE TITLE STEROID [ALTERNATIVE NAME: 3ß,6ß-diacet-oxy-5ß-methyl-19-norcholest-9(10)-ene], C31H50O4, confirms the generally accepted mechanism for the rearrangement of a cholestan-5α-ol derivative reported a century ago by Westphalen. The methyl group at position 10 of the starting material migrates to position 5 in the steroidal nucleus, while a Δ(9) bond is formed, as indicated by the C=C bond length of 1.347 (4) Å. The methyl transposition leaves the 5R configuration unchanged, with the methyl oriented towards the ß face. During the rearrangement, the steroidal B ring experiences a conformational distortion from chair to envelope with the C atom at position 6 as the flap. In the title structure, the isopropyl group of the side chain is disordered over two positions, with occupancies of 0.733 (10) and 0.267 (10). The carbonyl O atom in the acetyl group at C3 is also disordered with an occupancy ratio of 0.62 (4):0.38 (4).

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