Parthenolide (PTN) is a secondary metabolite of the plant Tanacetum parthenium (L.) Schulz Bip. and is considered the chemical marker of this species. This sesquiterpene lactone (germacrene skeleton) has been described as responsible for the biological activity of the leaf extract. In addition, several studies in the literature have demonstrated its antiparasitic and antineoplastic activity. However, there is a need for knowledge of other safety parameters, such as pharmacokinetic, pharmacodynamic and toxicity evaluations. Therefore, in this investigation, the in vitro metabolism of parthenolide was performed with rat liver microsomes and biomimetic metabolism (such as cytochrome P-450 system) using organometallic catalysts. The biomimetic procedure was validated since the major compound of biomimetic oxidative reaction with meta-chloroperbenzoic acid catalyzed by metalloporphyrin 5,10,15,20-tetrakis(pentafluorophenyl)-porphyrin iron(III) chloride was also observed with rat liver microsomes. Previous chemoenzymatic synthesis studies of PTN afforded the same epoxide formation, this major oxidative compound was isolated and fully characterized as (1 R,10R)-epoxyparthenolide based on experimental and theoretical calculations of infrared (IR) and vibrational circular dichroism (VCD) data at the B3PW91/6-311G. Furthermore, for the first time, this metabolite was evaluated for trypanocidal and leishmanicidal activity. The mean inhibitory concentration (IC50) values were lower for PTN than its metabolite and showed significant cytotoxic effects for both parasites. This finding holds promise for addressing neglected diseases. (PTN L. L (L. Bip species germacrene skeleton extract addition However parameters pharmacokinetic evaluations Therefore investigation P450 P 450 P-45 system catalysts metachloroperbenzoic meta chloroperbenzoic 5,10,15,20tetrakispentafluorophenylporphyrin 5101520tetrakispentafluorophenylporphyrin tetrakispentafluorophenylporphyrin 5,10,15,20 tetrakis pentafluorophenyl porphyrin 5 10 15 20 ironIII iron III iron(III formation 1 ( R,10Repoxyparthenolide R10Repoxyparthenolide RRepoxyparthenolide R,10R epoxyparthenolide R 10R IR (IR VCD (VCD B3PW91/6311G. B3PW916311G BPWG B3PW91/6 311G. B3PW91 6 311G B PW G B3PW91/6-311G Furthermore time IC50 IC (IC50 parasites diseases (L P45 45 P-4 20tetrakispentafluorophenylporphyrin 5101520 5,10,15,2 2 10Repoxyparthenolide Repoxyparthenolide R10R RR 6311G B3PW91/6311G B3PW916 BPW B3PW91/ B3PW9 IC5 (IC5 P4 4 P- 510152 5,10,15, B3PW (IC 51015 5,10,15 5101 5,10,1 510 5,10, 51 5,10 5,1 5,

RESUMO Objetivo Avaliar a precisão da tomografia corneana com imagens de Scheimpflug (Pentacam® AXL, OCULUS, Wetzlar, Alemanha) nos padrões de escaneamento com 25 e 50 imagens, verificando sua repetibilidade e reprodutibilidade em olhos normais, com ceratocone e com ceratocone após crosslinking. Métodos Estudo prospectivo, transversal, misto, no qual foram incluídos os pacientes que tinham córneas normais, ou com ceratocone; e não tinham realizado cirurgias corneanas, com exceção do crosslinking. Foram excluídos os pacientes que tivessem realizado outras cirurgias, como implante de anel intracorneano ou transplante de córnea. Foram realizadas três medidas com 25 imagens e três medidas com 50 imagens em cada olho incluído no estudo. Resultados O estudo avaliou 54 olhos de 41 pacientes. Destes, dez (18,52%) olhos eram com córneas normais e sem cirurgia ocular prévia aleatoriamente selecionados de 5 pacientes; 22 (40,74%) olhos aleatoriamente selecionados de 18 pacientes com ceratocone, sem cirurgia ocular prévia; e 22 (40,74%) olhos com ceratocone de 18 pacientes operados por crosslinking. No estudo da repetibilidade, percebemos uma maior variação de valores em todos os índices nos pacientes com ceratocone comparados aos de pacientes com olhos normais, em grande parte dos parâmetros analisados. Conclusão Não houve diferença significativa entre os métodos de escaneamento por 25 e 50 imagens, sendo o escaneamento por 25 imagens mais conveniente. A presença de ceratocone teve impacto negativo na repetibilidade de ambos os tipos de exame, e foi grande a concordância entre os métodos nos três grupos estudados. O coeficiente de repetibilidade permite considerar a relevância clínica dos dados para avaliar a progressão de ceratocone. Pentacam® Pentacam (Pentacam AXL OCULUS Wetzlar Alemanha 2 crosslinking prospectivo transversal misto corneanas córnea 4 Destes 18,52% 1852 52 (18,52% 40,74% 4074 40 74 (40,74% 1 analisados conveniente exame estudados 18,52 185 (18,52 40,74 407 7 (40,74 18,5 (18,5 40,7 (40,7 18, (18, 40, (40, (18 (40 (1 (4 (

ABSTRACT Objective To evaluate the accuracy of corneal tomography with Scheimpflug images (Pentacam® AXL, OCULUS, Wetzlar, Germany) in scanning patterns with 25 and 50 images, by analyzing their repeatability and reproducibility in normal eyes, eyes with keratoconus and with keratoconus after crosslinking. Methods Prospective, cross-sectional, mixed study including patients who had normal corneas, or who had keratoconus, who had not undergone corneal surgery, with the exception of crosslinking. Patients who had undergone surgery for intracorneal ring implantation or corneal transplantation were excluded. Three measurements were performed with 25 images and three measurements were performed with 50 images on each eye included in the study. Results The study evaluated a total of 54 eyes of 41 patients. Of these, 10 (18.52%) eyes had normal corneas, without previous eye surgery, 22 (40.74%) were eyes with keratoconus, without previous eye surgery, and 22 (40.74%) were eyes with keratoconus, with crosslinking for keratoconus. In the study of repeatability, we noticed a greater variation of values in all indices in patients with KC compared to those with normal eyes, in most of the parameters analyzed. Conclusion There is no significant difference between the scanning methods with 25 and 50 images. However, 25 scans has advantages that make it the main method suggested. The presence of keratoconus has a negative impact on the repeatability of both types of examination, and there is great agreement between the methods in the three groups studied. The high repeatability coefficient in some parameters suggests that these data should be used with care in the assessment of keratoconus progression. Pentacam® Pentacam (Pentacam AXL OCULUS Wetzlar Germany 2 5 Prospective crosssectional, crosssectional cross sectional, sectional cross-sectional corneas excluded 4 1 18.52% 1852 18 52 (18.52% 40.74% 4074 40 74 (40.74% analyzed However suggested examination studied progression 18.52 185 (18.52 40.74 407 7 (40.74 18.5 (18.5 40.7 (40.7 18. (18. 40. (40. (18 (40 (1 (4 (

The assignment of absolute configuration (AC) is a crucial step in the structural characterization of natural products, especially for those subjected to biological assays. Methods such as X-ray crystallography, stereocontrolled organic synthesis, nuclear magnetic resonance (NMR), and chiroptical spectroscopies are commonly used to determine the AC of chiral natural compounds. Even with these well-established techniques, however, unambiguous stereochemical assignments of natural products remain a challenge, resulting in an increasing number of structural misassignments being reported every year. Herein, we will present the main techniques that have been used in AC reassignments of natural products over the last 10 years, along with some selected examples. Special attention will be paid to the strengths and weaknesses of each approach. With this, we expect to provide the readers with critical information to help them to choose the appropriate methods for correct AC determinations.

The phytochemical study of Hippeastrum goianum led to the identification of 13 compounds by means of gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR). Compounds 7-demethoxy-9-O-methylhostasine (1) and 7-deoxi-trans-dihydronarciclasine (2) had their absolute configurations determined by vibrational circular dichroism (VCD). This is the first time that compound 1 is described in the Amaryllidaceae family. The cytotoxicity of all isolated compounds was tested against colorectal carcinoma (HCT 116), breast carcinoma (MCF-7), and non-tumor human retinal pigment epithelium (RPE) cell lines. The half-maximum inhibitory concentration (IC50) of compound 2 against each cell line was equivalent to the positive control (doxorubicin), indicating a considerable cytotoxic activity.

The antibiotic streptazolin (1), its E-isomer (2), along with the stereoisomers strepchazolin A (3) and strepchazolin B (4) and the inorganic compound cyclooctasulfur (5) were produced in solid culture by Streptomyces chartreusis ICBG377, which was isolated from the fungal garden of the leaf-cutter ant Acromyrmex subterraneus brunneus. This is the first time compound 2 is reported as a natural product. Compound 5, which showed antagonist activity against the specialized pathogenic fungus Escovopsis sp., was also produced by Streptomyces chartreusis ICBG323, isolated from the exoskeleton of winged male of Mycocepurus goeldii. The absolute configurations of 3 and 4 were confirmed by the combination of vibrational circular dichroism (VCD) spectroscopy and density functional theory (DFT) calculations. These results clearly demostrate the power of VCD to tell apart epimeric natural products. Compounds 1, 3 and 4 were produced by geographically distant but phylogenetically close strains, S. chartreusis ICBG 377 isolated in Brazil, and S. chartreusis NA02069, a marine sediment strain isolated in China.

Piper gaudichaudianum Kunth (Piperaceae) accumulates gaudichaudianic acid, a prenylated benzopyran, as its major component. Interestingly, this trypanocidal compound occurs as a racemic mixture. Herein, transcriptomic investigations of Piper gaudichaudianum using the RNA-seq approach are reported, and from the analysis of the transcripts expressed it was possible to propose a complete biosynthetic pathway for the production of gaudichaudianic acid, including the steps that originate its precursor, p-hydroxybenzoic acid. Peperomia obtusifolia (L.) A. Dietr. (Piperaceae) also accumulates racemic benzopyrans, however, its chromanes originate from the polyketide pathway, while the chromenes from Piper derives from the shikimate pathway. Recent transcriptomic and proteomic studies of the former species did not identify polyketide synthases involved in the production of the benzopyran moiety, but revealed the expression of tocopherol cyclase, which may be responsible for the cyclization of the 3,4-dihydro-2H-pyran ring. The analysis of the enzymes involved in the secondary metabolism of Piper gaudichaudianum and the comparison with the data previously obtained from Peperomia obtusifolia can provide valuable information on how these compounds are biosynthesized.

Abstract Composite structural elements of steel-concrete began to be used only in 1960 after the development of methods and constructive dispositions that ensured the functionality of these two materials together. In order to verify the importance of the participation of the axial mode in the frequency spectrum of the free vibration problem in composite beams with deformable shear connection, several analyses for 4 different boundary conditions and stiffness connection variation were performed. The analysis of the problem was carried out by development and computational implementation of a finite element for composite beams with partial interaction in the longitudinal direction applied to the problem of free vibrations. The solutions to this problem in the literature are scarce, and project recommendations are simplified. The results show that the finite element exhibits an excellent performance compared with the analytical results and as the axial mode has a high modal contribution, despite the boundary condition and stiffness connection.

This paper presents a finite element formulation for the numerical analysis of three-dimensional framed steel, reinforced concrete or composite steel and concrete structures subjected to fire. Several specialized and commercial programs may be used for the analysis of structures in fire condition. Within this context, the purpose of this work is to present the steps taken to extend a previously developed static analysis procedure with beam elements in order to cope with the thermal and structural analysis of structures under fire action. Physical nonlinearity and material property degradation considering the temperature distribution are taken into account at the cross section level, which is divided into quadrilateral or triangular finite elements. Thermal strains are considered through the effective strain concept, and the resulting nonlinear system of equations is solved by the Newton-Raphson scheme. The accuracy and capability of the formulation to simulate the behavior of framed structures under fire action are assessed through comparison with various numerical and experimental results.