3-Benzylaminomethyl Lithocholic Acid Derivatives Exhibited Potent and Selective Uncompetitive Inhibitory Activity Against Protein Tyrosine Phosphatase 1B (PTP1B).

Protein tyrosine phosphatase 1B (PTP1B) is a promising drug target for treating type 2 diabetes (T2DM) and obesity. As a result, developing new therapies that target PTP1B is an attractive strategy for treating these diseases. Herein, we detail the synthesis of 15 lithocholic acid (LA) derivatives, each containing different benzylaminomethyl groups attached to the C3 position of the steroid skeleton. The derivatives were assessed against two forms of PTP1B enzyme (hPTP1B1-400 and hPTP1B1-285), and the most potent compounds were then tested against T-cell protein tyrosine phosphatase (TCPTP) to determine their selectivity. The results showed that compounds 6m and 6n were more potent than the reference compounds (ursolic acid, chlorogenic acid, suramin, and TCS401). Additionally, both compounds exhibited greater potency over hPTP1B1-400. Furthermore, enzyme kinetic studies on hPTP1B1-400 revealed that these two lithocholic acid derivatives have an uncompetitive inhibition against hPTP1B1-400 with K i values of 2.5 and 3.4 µM, respectively. Interestingly, these compounds were around 75-fold more selective for PTP1B over TCPTP. Finally, docking studies and molecular dynamics simulations (MDS) were conducted to determine how these compounds interact with PTP1B. The docking studies revealed hydrophobic and H-bond interactions with amino acid residues in the unstructured region. MDS showed that these interactions persisted throughout the 200 ns simulation, indicating the crucial role of the unstructured zone in the biological activity and inhibition of PTP1B.

Hexane extract of Persea schiedeana Ness as green corrosion inhibitor for the brass immersed in 0.5 M HCl.

The hexane extract of Persea schiedeana Ness (PSN) was analyzed as corrosion inhibitor for the brass surface immersed in 0.5 M HCl. Fourier-transform infrared spectroscopy and a gas chromatographic (GC) and mass spectrometric (MS) were used to identify the PSN extract's functional groups and compound constituents. The functional groups identified were CH 3 and CH 2 functional alkyl groups, C=O stretching vibration of aldehydes, ketones, and carbonyl groups. The GC/MS determined the presence of fatty acids in the PSN extract, where palmitic acid, oleic acid, and ethyl oleate were the major constituents. Electrochemical characterizations were conducted to observe the effect of PSN as corrosion inhibitor on the brass surface. The Rp and Rn calculated from EIS and ENA give the same behavior. Based on the OCP behavior, it was determined that the PSN works as a mix inhibitor, affecting both anodic and cathodic reactions. The corrosion current density (Icorr) suggests that the extract of PSN reduces the corrosion rate of the brass with efficiencies above 90% for all concentrations. The efficiency obtained for each PSN concentration was attributed to forming a corrosion scale of CuO and Cu 2 O , which reacted with the carboxyl group to form copper carboxylates on the metal surface.

QSTR Modeling to Find Relevant DFT Descriptors Related to the Toxicity of Carbamates.

Compounds containing carbamate moieties and their derivatives can generate serious public health threats and environmental problems due their high potential toxicity. In this study, a quantitative structure-toxicity relationship (QSTR) model has been developed by using one hundred seventy-eight carbamate derivatives whose toxicities in rats (oral administration) have been evaluated. The QSRT model was rigorously validated by using either tested or untested compounds falling within the applicability domain of the model. A structure-based evaluation by docking from a series of carbamates with acetylcholinesterase (AChE) was carried out. The toxicity of carbamates was predicted using physicochemical, structural, and quantum molecular descriptors employing a DFT approach. A statistical treatment was developed; the QSRT model showed a determination coefficient (R2) and a leave-one-out coefficient (Q2LOO) of 0.6584 and 0.6289, respectively.

New QSPR model for prediction of corrosion inhibition using conceptual density functional theory.

The relationship between structure and corrosion inhibition of a series of twenty-eight quinoline and pyridine derivatives has been established through the investigation of quantum descriptors calculated with PBE/6-311 + + G** method. A quantitative structure-property relationship (QSPR) model was obtained by examining these descriptors using a genetic algorithm approximation method based on a multiple linear regression analysis. The results indicate that the efficiency of corrosion inhibitors is strongly associated with hardness (η), minimal electrostatic potential (ESPmin), and volume (V) descriptors. Furthermore, the validity of the proposed model is corroborated by an adsorption study on an iron surface Fe(110).

Nematicidal activity of furanoeremophilenes against Meloidogyne incognita and Nacobbus aberrans.

BACKGROUND: While searching for novel small molecules for new organic pesticide agents against plant-parasitic nematodes, we found that the hexane extract from the roots of Senecio sinuatos and its main secondary metabolite, 3ß-angeloyloxy-6ß-hydroxyfuranoeremophil-1(10)-ene (1), possess nematicidal activity against the second stage juvenile (J2) of Meloidogyne incognita and Nacobbus aberrans. Both species reduce yield of various vegetable crops. These results encouraged us to synthesize esters 3-9 formed by diol 2, obtained by alkaline hydrolysis of 1 and acetic anhydride, benzoic acid, 2-nitrobenzoic acid, 2-bromobenzoic acid, 4-nitrobenzoic acid, 4-bromobenzoic acid, and 4-methoxybenzoic acid, respectively. The nematicidal activity of these esters was evaluated and compared with that of the free benzoic acids. RESULTS: Natural product 1 and derivatives 2-9 were obtained and characterized by their physical and spectroscopic properties, including one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) experiments; X-ray diffraction analysis established their absolute configuration. The nematicidal activity of compounds 1-9 was assessed in vitro against M. incognita and N. aberrans J2 and was compared to activity shown by benzoic acid, 2-nitrobenzoic acid, 2-bromobenzoic acid, 4-nitrobenzoic acid, 4-bromobenzoic acid, and 4-methoxybenzoic acid. The esters suppressed nematodes more than free benzoic acid. Nacobbus aberrans J2 were suppressed, with compounds 5, 6, and 8 being the most active. CONCLUSION: Esters formed by 3ß,6ß-dihydroxyfuranoeremophil-1(10)-ene and ortho- or para-substituted benzoic acids containing electron acceptor groups had nematicidal activity against N. aberrans. These compound can potentially serve as a model for the development of new organic nematicidal agents. © 2022 Society of Chemical Industry.

A new computational model for the prediction of toxicity of phosphonate derivatives using QSPR.

Structural and electronic properties of a series of 25 phosphonate derivatives were analyzed applying density functional theory, with the exchange-correlation functional PBEPBE in combination with the 6-311++G** basis set for all atoms. The chemical reactivity of these derivatives has been interpreted using quantum descriptors such as frontier molecular orbitals (HOMO, LUMO), Hirshfeld charges, molecular electrostatic potential, and the dual descriptor [[Formula: see text]]. These descriptors are directly related to experimental median lethal dose ([Formula: see text], expressed as its decimal logarithm [[Formula: see text]([Formula: see text]] through a multiple linear regression equation. The proposed model predicts the toxicity of phosphonates in function of the volume (V), the load of the most electronegative atom of the molecule (q), and the eigenvalue of the molecular orbital HOMO ([Formula: see text]. The obtained values in the internal validation of the model are: [Formula: see text]%, [Formula: see text]%, [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text]%. The toxicity of nine phosphonate derivatives used as test molecules was adequately predicted by the model. The theoretical results indicate that the oxygen atom of the O=P group plays an important role in the interaction mechanism between the phosphonate and the acetylcholinesterase enzyme, inhibiting the removal of the proton of the ser-200 residue by the his-440 residue.

From metallic gold to [Au(NHC)2]+ complexes: an easy, one-pot method.

A simple and direct method is described to prepare cationic bis(NHC)-Au(i) complexes containing N-alkyl or N-aryl NHC ligands to generate relevant gold complexes using metallic gold as the starting material.

Revisional Surgery Following Laparoscopic Gastric Plication.

BACKGROUND: The laparoscopic gastric plication (LGP) is a relative new bariatric procedure that has gained popularity over the last few years, but no real consensus exists and the evidence is unclear, especially in its real efficacy, safety, and durability. METHODS: Retrospective study analyzing the records patients submitted to LGP between 2009 and 2010. The primary objective was to describe the characteristics and outcomes of patients submitted to revisional surgery. Baseline data and evolution were obtained and analyzed. Surgical analysis included revision cause, perioperative outcome, type of surgery, complications, and weight loss after 18 months. A comparison between gastric bypass and sleeve gastrectomy was performed. RESULTS: One hundred LGP were performed. After a mean time of 13.5 months, 42 patients presented an overall excess weight loss (EWL) <50 % and 38 had severe symptoms. Thirty patients accepted revisional surgery with BMI before conversion of 38.6 ± 4.2 kg/m2. There were 17 laparoscopic sleeve gastrectomy (LSG) and 13 laparoscopic gastric bypass (LGBP) with comparable preoperative characteristics. The LSG group had lower pneumoperitoneum time and less hospital stay. At 18 months, the LGBP group had lower BMI (24.1 ± 1.1 vs. 25.8 ± 1.3 kg/m2 for the LSG; p = 0.006) and higher %EWL (75.7 ± 16.1 vs. 61.4 ± 14.5 % for the LSG; p = 0.008). CONCLUSION: In our series, LGP presented a high failure rate and an increased number of symptomatic patients. Revisional surgery proved to be safe and effective. Revision to LSG was faster and had less hospital stay. Revision to LGBP showed better %EWL at 18 months.

Reduced density gradient as a novel approach for estimating QSAR descriptors, and its application to 1, 4-dihydropyridine derivatives with potential antihypertensive effects.

The relationship between the chemical structure and biological activity (log IC50) of 40 derivatives of 1,4-dihydropyridines (DHPs) was studied using density functional theory (DFT) and multiple linear regression analysis methods. With the aim of improving the quantitative structure-activity relationship (QSAR) model, the reduced density gradient s( r) of the optimized equilibrium geometries was used as a descriptor to include weak non-covalent interactions. The QSAR model highlights the correlation between the log IC50 with highest molecular orbital energy (E HOMO), molecular volume (V), partition coefficient (log P), non-covalent interactions NCI(H4-G) and the dual descriptor [Δf(r)]. The model yielded values of R 2=79.57 and Q 2=69.67 that were validated with the next four internal analytical validations DK=0.076, DQ=-0.006, R P =0.056, and R N=0.000, and the external validation Q 2boot=64.26. The QSAR model found can be used to estimate biological activity with high reliability in new compounds based on a DHP series. Graphical abstract The good correlation between the log IC50 with the NCI (H4-G) estimated by the reduced density gradient approach of the DHP derivatives.

Morbimortalidad por síndrome de broncoaspiración meconial en recién nacidos de un hospital público del estado Cojedes: Venezuela / Morbidity and mortality by meconium aspiration syndrome in newborns of Cojedes state public hospital: Venezuela

Normalmente el meconio es la primera excreción intestinal del recién nacido, está compuesto por células epiteliales, pelo fetal, moco y bilis. El estrés intrauterino puede causar evacuación in útero de meconio hacia el líquido amniótico el cual puede ser aspirado por el feto in útero o por el recién nacido durante el trabajo de parto. La aspiración del meconio puede causar obstrucción de la vía aérea y reacción inflamatoria intensa, lo que determinará dificultad respiratoria severa. La presencia de meconio en el líquido amniótico es un signo que advierte sufrimiento fetal y exige una supervisión cuidadosa del trabajo de parto con adecuada evaluación de la salud fetal. En atención a ello se planteo como objetivo del estudio, conocer la frecuencia del síndrome de broncoaspiración meconial en un hospital público, y establecer factores de riesgo asociados a su aparición. Se realizo una investigación de tipo descriptivo, transversal y de campo, en el servicio de neonatología de un hospital público del Estado Cojedes. Fue seleccionada una muestra no probabilística intencional, siendo evaluados 71 recién nacidos vivos que presentaron Síndrome de Dificultad Respiratoria. Los resultados reportaron que 13% de los sujetos presentaron el síndrome. La mortalidad fue de 44,4% causada por dificultad respiratoria. Los factores de riesgo predominantes fueron: expulsivo prolongado 44,4%, ruptura prematura de membrana 22,2% y traumatismo durante el parto 22,2%. Se concluye que la frecuencia y mortalidad elevada por esta condición, se encuentra asociado a factores de riesgo altamente prevenibles.

The violence constitutes one of the high-priority problems in America currently and together with the insecurity, they occupy the first place in the civic concern in most of the countries, Venezuela has been investing in security`s public politics, while the mortality for violent facts has had a tendency to increase in the last ten years. Exploring some answers was carried out a correlacional study with the purpose of looking for associations among the mortality for homicides, with socio-political variables that could be influencing in the behavior of the violent facts in the Aragua State. The results indicates the education investment influences the behavior of this mortality with 72,4%. Paradoxically, it was observed a coefficient of positive Pearson and a direct moderate (p = 0,05) correlation. 59,8% of the behavior of the mortality for the violent facts. This can be explained by the inefficacy of the developed security strategies and the current penal legislation. It concludes the behavior of the mortality for the violent facts of Aragua state. have been associated with the quality of the educational strategies and the police and repressive focus of the security politics carried out in region.

Neumonitis por hipersensibilidad en la ciudad de México / hypersensitivity pneumonitis in Mexico City

Objetivo. Determinar la asociación entre la zona urbana de origen del paciente en la ciudad de México y la prevalencia de neumonitis por hipersensibilidad inducida por antígeno aviario. Material y métodos. Se trata de un estudio de casos y controles realizado en el Instituto Nacional de Enfermedades Respiratorias, en la ciudad de México, en el año de 1999. Se estudiaron 109 casos con neumonitis por hipersensibilidad y 184 controles: de éstos, 39, con fibrosis pulmonar idiopática; 63, con tuberculosis pulmonar, y 82, con asma. La ciudad de México y las zonas conurbadas se dividieron en cinco zonas geográficas: centro, noreste, sureste, noroeste y el suroeste. Se calcularon las prevalencias de las diferentes enfermedades por zona urbana de los pacientes que participaron en el estudio; como medida de asociación, se estimó la razón de momios, con un intervalo de confianza al 95 por ciento. Asimismo, se realizó regresión logística múltiple ajustando por edad, sexo y estrato socioeconómico. Resultados. Ochenta casos de neumonitis por hipersensibilidad se concentraron en el sur del noreste de las zonas conurbadas y la parte norte del sureste de la ciudad de México, 48 y 32, respectivamente (RM= 3.86, IC 95 por ciento 2.17-6.96). Treinta y seis controles de asma se localizaron en el suroeste de la ciudad de México, zona donde se ubica el Intituto Nacional de Enfermedades Respiratorias (p<0.05) y cuatro en la zona co-nurbada. Los controles de tuberculosis pulmonar y fibrosis pulmonar idiopática estuvieron dispersos en la ciudad de México y en las zonas conurbadas. Conclusiones. La zona sur del noreste y el norte de la sureste están asociadas a la neumonitis por hipersensibilidad. Las causas de esta asociación no parece ser geográfica, pero existe el antecedente de que esa zona fue basurero de la ciudad, por lo que partículas orgánicas en el ambiente pudieran coadyuvar a la aparición de esta enfermedad.

Muerte súbita cardíaca: ¿Después de la reanimación qué? Evolución hospitalaria y post-hospitalaria de pacientes resucitados fuera del hospital de un episodio de muerte súbita de origen cardíaco / e

La muerte súbita de origen cardíaco es una de las formas de muerte más comunes y constituye un problema de salud pública aún no resuelto por la medicina moderna. En nuestro país existe una estructura de servicios de emergencia extrahospitalaria y de centros de tratamiento intensivo muy desarrollada dedicada a la reanimación de los pacientes que sufren de un episodio de muerte súbita cardíaca; sin embargo no existen datos publicados sobre la evolución de estos pacientes luego de ingresar al hospital. El objetivo de este trabajo es conocer la evolución a largo plazo de los pacientes con muerte súbita abortada que llegan vivos al hospital. Se analizaron retrospectivamente la historia de 24 pacientes ingresados a un CTI polivalente luego de reanimados de un episodio de muerte súbita cardíaca durante el año 1989. 11/24 pacientes (46 por ciento) fallecieron en el hospital debido a agravio encefálico y shock cardiogénico. 4/13 pacientes egresados vivos fallecieron durante el seguimiento (3l por ciento). En 18/24 pacientes el mecanismo de la muerte súbita fue fibrilación ventricular, estando en 10/18 vinculada a un infarto agudo de miocardio. 87 por ciento de los pacientes presentaban evidencias clínicas de coronariopatía (21/24). El análisis de esta serie confirma la alta mortalidad hospitalaria y post-hospitalaria de los pacientes resucitados de un episodio de muerte súbita fuera del hospital, la alta incidencia de cardiopatía isquémica como patología de fondo y la fibrilación ventricular como mecanismo dominante de muerte súbita(AU)