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The (R,R)-Teth-TsDPEN-Ru(II) complex promoted the one-pot double C=O reduction of α-alkyl-ß-ketoaldehydes through asymmetric transfer hydrogenation/dynamic kinetic resolution (ATH-DKR) under mild conditions. In this process, ten anti-2-benzyl-1-phenylpropane-1,3-diols (85:15 to 92:8 dr) were obtained in good yields (41-87%) and excellent enantioselectivities (>99% ee for all compounds). Notably, the preferential reduction of the aldehyde moiety led to the in situ formation of 2-benzyl-3-hydroxy-1-phenylpropan-1-one intermediates. These intermediates played a crucial role in enhancing both reactivity and stereoselectivity through hydrogen bonding.

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Objective.Accurate simulation of human tissues is imperative for advancements in diagnostic imaging, particularly in the fields of dosimetry and image quality evaluation. Developing Tissue Equivalent Materials (TEMs) with radiological characteristics akin to those of human tissues is essential for ensuring the reliability and relevance of imaging studies. This study presents the development of a mathematical model and a new toolkit (TEMPy) for obtaining the best composition of materials that mimic the radiological characteristics of human tissues. The model and the toolkit are described, along with an example showcasing its application to obtain desired TEMs.Approach.The methodology consisted of fitting volume fractions of the components of TEM in order to determine its linear attenuation coefficient as close as possible to the linear attenuation coefficient of the reference material. The fitting procedure adopted a modified Least Square Method including a weight function. This function reflects the contribution of the x-ray spectra in the suitable energy range of interest. TEMPy can also be used to estimate the effective atomic number and electron density of the resulting TEM.Main results.TEMPy was used to obtain the chemical composition of materials equivalent to water and soft tissue, in the energy range used in x-ray imaging (10 -150 keV) and for breast tissue using the energy range (5-40 keV). The maximum relative difference between the linear attenuation coefficients of the developed and reference materials was ±5% in the considered energy ranges.Significance.TEMPy facilitates the formulation of TEMs with radiological properties closely mimicking those of real tissues, aiding in the preparation of physical anthropomorphic or geometric phantoms for various applications. The toolkit is freely available to interested readers.

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Rearranged homoisoflavonoids constitute a unique group of natural products, renowned for their structural diversity and complexity. These compounds, derived from modifications in the 3-benzylchroman skeleton, are categorized into four subclasses: brazilin, caesalpin, protosappanin, and scillascillin homoisoflavonoids. This review examines the advancements in the total synthesis of these complex structures, aiming to highlight the challenges and opportunities encountered. A comparative analysis of the strategies employed thus far to synthesize these compounds provides a comprehensive understanding of the progress in this field.

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BACKGROUND: Leukemias stand out for being the main type of childhood cancer in the world. Current treatments have strong side effects for patients, and there is still a high rate of development of resistance to multidrug therapy. Previously, our research group developed a structure-activity study with novel synthetic molecules analogous to LQB-278, described as an essential molecule with in vitro antileukemic action. Among these analogs, LQB-461 stood out, presenting more significant antileukemic action compared to its derivative LQB-278, with cytostatic and cytotoxicity effect by apoptosis, inducing caspase-3, and increased sub-G1 phase on cell cycle analysis. METHODS AND RESULTS: Deepening the study of the mechanism of action of LQB-461 in Jurkat cells in vitro, a microarray assay was carried out, which confirmed the importance of the apoptosis pathway in the LQB-461 activity. Through real-time PCR, we validated an increased expression of CDKN1A and BAX genes, essential mediators of the apoptosis intrinsic pathway. Through the extrinsic apoptosis pathway, we found an increased expression of the Fas receptor by flow cytometry, showing the presence of a more sensitive population and another more resistant to death. Considering the importance of autophagy in cellular resistance, it was demonstrated by western blotting that LQB-461 decreased LC-3 protein expression, an autophagic marker. CONCLUSIONS: These results suggest that this synthetic molecule LQB-461 induces cell death by apoptosis in Jurkat cells through intrinsic and extrinsic pathways and inhibits autophagy, overcoming some mechanisms of cell resistance related to this process, which differentiates LQB-461 of other drugs used for the leukemia treatment.

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Background: Obesity poses a major risk for cardiovascular diseases, while it is almost a consensus that intra-abdominal adiposity has a more deleterious effect for metabolic syndrome. In this sense, it is speculated that lipectomy or liposuction would be metabolically harmful, as it changes the abdominal-superficial adipose tissue ratio. However, the literature has shown conflicting evidence. Methods: In order to evaluate the possibility of metabolism alteration resulting from body coutouring surgery, a prospective cohort was implemented with 35 patients who underwent abdominoplasty, including some with a history of massive weight loss. Fasting blood glucose, fasting plasma insulin, triglycerides, total cholesterol and fractions were requested preoperatively and in the third postoperative month. The groups were also compared with each other. Results: No statistically significant variation between the exams collected in the preoperative period and those collected after abdominoplasty was found. There was a statistically significant difference in LDL (low-density lipoprotein; p = 0.033) and non-HDL (non-high-density lipoprotein) cholesterol (p = 0.020) between the two control tests of the groups surveyed. There were also differences in comorbidities (p = 0.006) and complications (p <0.001) between the groups. Conclusions: Abdominoplasty was not able of changing tests that assess glycemic and lipid metabolism three months after the operation. Our attention was drawn to the fact that patients who had massive weight loss had better control of LDL cholesterol (p = 0.033) and non-HDL cholesterol (p = 0.020), despite having higher weight and body mass index (p <0.001).

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The oxo-tethered-Ru(II) precatalyst promoted the one-pot C═C/C═O reduction of chalcones using sodium formate as the hydrogen source in water through asymmetric transfer hydrogenation. Twenty-seven 1,3-diarylpropan-1-ols were obtained in good to excellent yields (up to 96%) and enantiomeric purities (up to 98:2). Our data suggested that the enones are first reduced to the corresponding dihydrochalcones (1,4-selectivity) and then into 1,3-diarylpropan-1-ols (C═O reduction). The stereoelectronic effects of electron-donating and electron-withdrawing groups at the ortho, meta and para positions of both aromatic rings were evaluated. The 2-OH group at the B ring was well tolerated, allowing a straightforward enantioselective synthesis of two flavans through the Mitsunobu cyclization, the antiviral (S)-BW683C and the natural flavan (S)-tephrowatsin E.

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PURPOSE: A Monte Carlo (MC) modeling of single axial and helical CT scan modes has been developed to compute single and accumulated dose distributions. The radiation emission characteristics of an MDCT scanner has been modeled and used to evaluate the dose deposition in infinitely long head and body PMMA phantoms. The simulated accumulated dose distributions determined the approach to equilibrium function, H(L). From these H ( L ) curves, dose-related information was calculated for different head and body clinical protocols. METHODS: The PENELOPE/penEasy package has been used to model the single axial and helical procedures and the radiation transport of photons and electrons in the phantoms. The bowtie filters, heel effect, focal-spot angle, and fan-beam geometry were incorporated. Head and body protocols with different pitch values were modeled for x-ray spectra corresponding to 80, 100, 120, and 140 kV. The analytical formulation for the single dose distributions and experimental measurements of single and accumulated dose distributions were employed to validate the MC results. The experimental dose distributions were measured with OSLDs and a thimble ion chamber inserted into PMMA phantoms. Also, the experimental values of the C T D I 100 along the center and peripheral axes of the CTDI phantom served to calibrate the simulated single and accumulated dose distributions. RESULTS: The match of the simulated dose distributions with the reference data supports the correct modeling of the heel effect and the radiation transport in the phantom material reflected in the tails of the dose distributions. The validation of the x-ray source model was done comparing the CTDI ratios between simulated, measured and CTDosimetry data. The average difference of these ratios for head and body protocols between the simulated and measured data was in the range of 13-17% and between simulated and CTDosimetry data varied 10-13%. The distributions of simulated doses and those measured with the thimble ion chamber are compatible within 3%. In this study, it was demonstrated that the efficiencies of the C T D I 100 measurements in head phantoms with nT = 20 mm and 120 kV are 80.6% and 87.8% at central and peripheral axes, respectively. In the body phantoms with n T = 40 mm and 120 kV, the efficiencies are 56.5% and 86.2% at central and peripheral axes, respectively. In general terms, the clinical parameters such as pitch, beam intensity, and voltage affect the Deq values with the increase of the pitch decreasing the Deq and the beam intensity and the voltage increasing its value. The H(L) function does not change with the pitch values, but depends on the phantom axis (central or peripheral). CONCLUSIONS: The computation of the pitch-equilibrium dose product, D ̂ eq , evidenced the limitations of the C T D I 100 method to determine the dose delivered by a CT scanner. Therefore, quantities derived from the C T D I 100 propagate this limitation. The developed MC model shows excellent compatibility with both measurements and literature quantities defined by AAPM Reports 111 and 200. These results demonstrate the robustness and versatility of the proposed modeling method.

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BACKGROUND/AIM: A new set of LQB-nitrones and analogues was synthesized to evaluate anticancer activity based on the substitution of the terpenyl moiety of the antileukemic compound LQB-278 by the conformationally restricted cinnamyl ether. MATERIALS AND METHODS: A structure-activity relationship study was performed in vitro on Jurkat cells to screen the antileukemic activity of LQB-nitrones and analogues and elucidate the mechanisms of action of the most active derivatives. RESULTS: The cynamyl ramification and its ortho position aldehyde substitution improved the antileukemic activity. Three compounds showed an in vitro antiproliferative action, but only 5b induced apoptosis. Analysis of the molecular mechanisms showed increased expression of the cell cycle inhibitor p21CIP1/WAF1/Sdi1, caspase 3, Fas receptor, and Bax/Bcl-2 ratio. CONCLUSION: The cinnamyl derivative 5b (LQB-461) presented higher antileukemic effects than the prototype terpenyl nitrone, inducing Jurkat cell death by activating both extrinsic and intrinsic pathways of apoptosis. Therefore, this compound is a new promising candidate drug against leukemia.

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5-Nitro-furan nitrones (1) and 5-nitro-thiophene nitrones (2) were synthesized in one step. Compounds 1a-c had the most potent leishmanicidal activity against intracellular amastigote forms of Leishmania amazonensis and L. infantum (from 0.019 to 2.76 µM), with excellent selectivity (from 39 to 5673). The comparison of the leishmanicidal activity in promastigotes of wild type L. donovani with those overexpressing nitroreductases NRT1 or NRT2 shows that 1a,b are activated by both, which could slow the development of resistance. Their redox potential (E redox) obtained by cyclic voltammetry (-0.67 and -0.62 V) shows that the reduction of the nitro group is modulated by the nitrone group. Oral administration of 1b to mice infected by L. infantum reduced the parasite load on the spleen by 76.6 and 95.0% with doses of 50 and 100 mg/kg, respectively, administered twice a day, for 5 days. In the liver, the parasite load suppression was above 75% with either treatment.

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The synthesis of nitrogen-containing heterocycles, including natural alkaloids and other compounds presenting different types of biological activities have proved to be successful employing chiral sulfinyl imines derived from tert-butanesulfinamide. These imines are versatile chiral auxiliaries and have been extensively used as eletrophiles in a wide range of reactions. The electron-withdrawing sulfinyl group facilitates the nucleophilic addition of organometallic compounds to the iminic carbon with high diastereoisomeric excess and the free amines obtained after an easy removal of the tert-butanesulfinyl group can be transformed into enantioenriched nitrogen-containing heterocycles. The goal of this review is to the highlight enantioselective syntheses of heterocycles involving the use of chiral N-tert-butanesulfinyl imines as reaction intermediates, including the synthesis of several natural products. The synthesis of nitrogen-containing heterocycles in which the nitrogen atom is not provided by the chiral imine will not be considered in this review. The sections are organized according to the size of the heterocycles. The present work will comprehensively cover the most pertinent contributions to this research area from 2012 to 2020. We regret in advance that some contributions are excluded in order to maintain a concise format.