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The marine kingdom is an important source of a huge variety of scaffolds inspiring the design of new drugs. The complex molecules found in the oceans present a great challenge to organic and medicinal chemists. However, the wide variety of biological activities they can display is worth the effort. In this article, we present an overview of different seaweeds as potential sources of bioactive pigments with activity against neurodegenerative diseases, especially due to their neuroprotective effects. Along with a broad introduction to seaweed as a source of bioactive pigments, this review is especially focused on astaxanthin and fucoxanthin as potential neuroprotective and/or anti-neurodegenerative agents. PubMed and SciFinder were used as the main sources to search and select the most relevant scientific articles within the field.

El trabajo presenta la experiencia desarrollada en el diseño e implementación de un entrenamiento en línea del posgrado de la Universidad Central “Marta Abreu” de Las Villas, Cuba. A partir de las posibilidades tecnológicas de la plataforma instalada en la institución se realizó este entrenamiento sobre la publicación de artículos en revistas educativas. La metodología se enmarcó dentro del enfoque cualitativo y se utilizó el diseño metodológico de investigación-acción durante las dos etapas que abarcó este proceso. Como resultado del trabajo desplegado se elaboró el diseño del entrenamiento, que se construyó a lo largo del proceso investigativo y comprobó su funcionalidad en las condiciones de la infraestructura tecnológica de la universidad. En general, se considera que la experiencia fue positiva y que puede constituir una vía para elevar la preparación de los docentes de la propia universidad y de otras instituciones de Educación Superior en lo que respecta a la producción y comunicación científica y, así, aprovechar las oportunidades que brindan los espacios virtuales de aprendizaje.= The work presents the experience developed in the Central University “Marta Abreu” of the Villas, Cuba, in the design and implementation of postgraduate online training about the publication of articles in educative journals considering the technological possibilities of the platform installed in the institution. The methodology followed was framed within the qualitative approach, and the research-action design was used during the two stages that the research included. As a result, the design of the online training was elaborated throughout the research process and its functionality in the conditions of the technological infrastructure of the university was verified. In general, the experience was considered positive and it can constitute a way to elevate the preparation of teachers of the university and other institutions of Higher Education, with regard to the scientific production and communication, taking advantage of the opportunities that the virtual spaces of learning offer.

Coumarin is a privilege scaffold in medicinal chemistry. Coumarin derivatives are still an emerging class of highly potent pharmaceutical drugs, best known in the field of antimicrobials and anticoagulants. Thiocoumarins are a particular class of coumarins in which one or two of the oxygen atoms are replaced by a sulfur. They are chemically subdivided in three groups: Thiocoumarins, 2-thioxocoumarins, and dithiocoumarins. This review emphasizes the rationale behind the synthesis and biological applications of the most relevant publications related to this family of compounds. Particular attention has been given to their potential as drug candidates, with particular emphasis in the last 5 years. This article is based on the most relevant information collected from multiple electronic databases, including SciFinder, Pubmed, Espacenet, and Mendeley.

3-Phenylcoumarins are a family of heterocyclic molecules that are widely used in both organic and medicinal chemistry. In this overview, research on this scaffold, since 2010, is included and discussed, focusing on aspects related to its natural origin, synthetic procedures and pharmacological applications. This review paper is based on the most relevant literature related to the role of 3-phenylcoumarins in the design of new drug candidates. The references presented in this review have been collected from multiple electronic databases, including SciFinder, Pubmed and Mendeley.

Coumarins are naturally occurring molecules with a versatile range of activities. Their structural and physicochemical characteristics make them a privileged scaffold in medicinal chemistry and chemical biology. Many research articles and reviews compile information on this important family of compounds. In this overview, the most recent research papers and reviews from 2020 are organized and analyzed, and a discussion on these data is included. Multiple electronic databases were scanned, including SciFinder, Mendeley, and PubMed, the latter being the main source of information. Particular attention was paid to the potential of coumarins as an important scaffold in drug design, as well as fluorescent probes for decaging of prodrugs, metal detection, and diagnostic purposes. Herein we do an analysis of the trending topics related to coumarin and its derivatives in the broad field of drug discovery.

Introducción: El cáncer de vejiga, representa el segundo tumor más frecuente en el tracto genital. El adenocarcinoma constituye de 0,5 a 2% de los tumores vesicales. Desde el punto de vista histológico los adenocarcinomas son mucosecretantes y pueden tener patrones glandulares, coloides o de células en anillo de sello. A pesar de los avances logrados en el tratamiento del carcinoma de vejiga, tumores infrecuentes como el adenocarcinoma vesical, no tienen un tratamiento y control estandarizado de la enfermedad. Objetivo: Presentar un caso de una paciente portadora de un adenocarcinoma primario de vejiga de células en anillo de sello, enfermedad rara y de muy mal pronóstico. Presentación del caso: Se presenta un caso de una paciente de 60 años, con antecedentes de hipertensión arterial, con un adenocarcinoma en células de anillo primario de vejiga, tratada por un equipo multidisciplinario, intervenida quirúrgicamente con una evolución favorable. Se hace una revisión actualizada de la enfermedad. Conclusiones: Se presenta un caso muy infrecuente en la práctica clínica. Una paciente intervenida quirúrgicamente por adenocarcinoma en células de anillo primario de vejiga, que evolucionó favorablemente. El tratamiento de esta enfermedad, no se encuentra estandarizado y la intervención multidisciplinaria de estos pacientes constituye la mejor opción terapéutica. No se encontró reporte de otro caso tratado en Cuba. Palabras clave: Adenocarcinoma, carcinoma, células en anillo de sello; tumores vesicales, tumor en tracto genital.

In the present work we synthesized a selected series of hydroxylated 3-phenylcoumarins 5–8, with the aim of evaluating in detail their antioxidant properties. From an in depth study of the antioxidant capacity data (ORAC-FL, ESR, CV and ROS inhibition) it was concluded that these derivatives are very good antioxidants, with very interesting profiles in all the performed assays. The study of the effect of the number and position of the hydroxyl groups on the antioxidant activity was the principal aim of this study. In particular, 7-hydroxy-3-(3'-hydroxy)phenylcoumarin (8) proved to be the most active and effective antioxidant of the selected series in four of the performed assays (ORAC-FL = 11.8, capacity of scavenging hydroxyl radicals = 54%, Trolox index = 2.33 and AI30 index = 0.18). However, the presence of two hydroxyl groups on this molecule did not increase greatly the activity profile. Theoretical evaluation of ADME properties of all the derivatives was also carried out. All the compounds can act as potential candidates for preventing or minimizing the free radical overproduction in oxidative-stress related diseases. These preliminary findings encourage us to perform a future structural optimization of this family of compounds.

Antibiotic resistance is one of the main public health concerns of this century. This resistance is also associated with oxidative stress, which could contribute to the selection of resistant bacterial strains. Bearing this in mind, and considering that flavonoid compounds are well known for displaying both activities, we investigated a series of hydroxy-3-arylcoumarins with structural features of flavonoids for their antibacterial activity against different bacterial strains. Active compounds showed selectivity against the studied Gram-positive bacteria compared to Gram-negative bacteria. 5,7-Dihydroxy-3-phenylcoumarin (compound 8) displayed the best antibacterial activity against Staphylococcus aureus and Bacillus cereus with minimum inhibitory concentrations (MICs) of 11 μg/mL, followed by Staphylococcus aureus (MRSA strain) and Listeria monocytogenes with MICs of 22 and 44 μg/mL, respectively. Moreover, molecular docking studies performed on the most active compounds against Staphylococcus aureus tyrosyl-tRNA synthetase and topoisomerase II DNA gyrase revealed the potential binding mode of the ligands to the site of the appropriate targets. Preliminary structure−activity relationship studies showed that the antibacterial activity can be modulated by the presence of the 3-phenyl ring and by the position of the hydroxyl groups at the coumarin scaffold.

Neurodegenerative diseases are becoming increasingly prevalent with the aging of the generalpopulation [...]

A new series of amino/nitro-substituted 3-arylcoumarins were synthesized and their antibacterial activity against clinical isolates of Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative) was evaluated. Some of these molecules exhibited antibacterial activity against S. aureus comparable to the standards used (oxolinic acid and ampicillin). The preliminary structure-activity relationship (SAR) study showed that the antibacterial activity against S. aureus depends on the position of the 3-arylcoumarin substitution pattern. With the aim of finding the structural features for the antibacterial activity and selectivity, in the present manuscript different positions of nitro, methyl, methoxy, amino and bromo substituents on the 3-arylcoumarin scaffold were reported.

A series of 6-halo-3-hydroxyphenylcoumarins (resveratrol-coumarins hybrid derivatives) was synthesized in good yields by a Perkin reaction followed by hydrolysis. The new compounds were evaluated for their vasorelaxant activity in intact rat aorta rings pre-contracted with phenylephrine (PE), as well as for their inhibitory effects on platelet aggregation induced by thrombin in washed human platelets. These compounds concentration-dependently relaxed vascular smooth muscle and some of them showed a platelet antiaggregatory activity that was up to thirty times higher than that shown by trans-resveratrol and some other previously synthesized derivatives.

In the present work we report on the contribution of the coumarin moiety to tyrosinase inhibition. Coumarin-resveratrol hybrids 1-8 have been resynthesized to investigate the structure-activity relationships and the IC50 values of these compounds were measured. The results showed that these compounds exhibited tyrosinase inhibitory activity. Compound 3-(3’,4’,5’-trihydroxyphenyl)-6,8-dihydroxycoumarin (8)is the most potentcompound (0.27 mM), more so than umbelliferone (0.42 mM), used as reference compound. The kinetic studies revealed that compound 8 caused non-competitive tyrosinase inhibition.

In the title coumarin derivative (also known as 2H-chromen-2-one or 2H-1-benzopyran-2-one), C17H11NO6, the coumarin ring system is nearly planar, with a dihedral angle of 3.35 (9)° between the pyrone and the benzene rings. The dihedral angle between the planes formed by the coumarin ring system and the benzene substituent is 54.60 (7)°, clearly showing the non-coplanarity of the whole aromatic system. The crystal studied was a non-merohedral twin; the minor component refined to approximately 0.44.

Leishmaniasis is a growing health problem worldwide. As there are certain drawbacks with the drugs currently used to treat human leishmaniasis and resistance to these drugs is emerging, there is a need to develop novel antileishmanial compounds, among which isoquinoline alkaloids are promising candidates. In this study, 18 novel oxoisoaporphine derivatives were synthesized and their possible antileishmanial activity was evaluated. The in vitro activity of these derivatives against Leishmania amazonensis axenic amastigotes was first evaluated, and the selected compounds were then tested in an inhibition assay with promastigotes of L. infantum, L. braziliensis, L. amazonensis and L. guyanensis, and with intracellular amastigotes of L. infantum and L. amazonensis. Finally, the most active compounds, OXO 1 (2,3-dihydro-7H-dibenzo[de,h]quinolin-7-one) and OXO 13 (2,3,8,9,10,11-hexahydro-7H-dibenzo[de,h]quinolin-7-one), were tested in BALB/c mice infected with L. infantum. Treatment of mice at a dose of 10 mg/kg with OXO 1 yielded significant reductions (p

Drug-drug interactions (DDIs) constitute an important problem in postmarketing pharmacovigilance and in the development of new drugs. The effectiveness or toxicity of a medication could be affected by the co-administration of other drugs that share pharmacokinetic or pharmacodynamic pathways. For this reason, a great effort is being made to develop new methodologies to detect and assess DDIs. In this article, we present a novel method based on drug interaction profile fingerprints (IPFs) with successful application to DDI detection. IPFs were generated based on the DrugBank database, which provided 9,454 well-established DDIs as a primary source of interaction data. The model uses IPFs to measure the similarity of pairs of drugs and generates new putative DDIs from the non-intersecting interactions of a pair. We described as part of our analysis the pharmacological and biological effects associated with the putative interactions; for example, the interaction between haloperidol and dicyclomine can cause increased risk of psychosis and tardive dyskinesia. First, we evaluated the method through hold-out validation and then by using four independent test sets that did not overlap with DrugBank. Precision for the test sets ranged from 0.4-0.5 with more than two fold enrichment factor enhancement. In conclusion, we demonstrated the usefulness of the method in pharmacovigilance as a DDI predictor, and created a dataset of potential DDIs, highlighting the etiology or pharmacological effect of the DDI, and providing an exploratory tool to facilitate decision support in DDI detection and patient safety.

In the title compound, C16H17NO3, the coumarin moiety is essentially planar [maximum deviation from the mean plane formed by the C and O atoms of the coumarin = 0.0183 (12) Å] and that the cyclohexane ring adopts the usual chair conformation. The dihedral angle between the mean plane of the coumarin residue and the plane of the amide residue (defined as the N, C and O atoms) is 18.9 (2)°. There are two intramolecular hydrogen bonds involving the amide group. In one, the N atom acts as donor to the ketonic O atom and in the other, the amide O atom acts as acceptor of a C—H group of the coumarin. In the crystal, molecules are linked into inversion dimers by pairs of N—H...O contacts and these dimers are linked into pairs by weak C—H...O hydrogen bonds. The combination of these interactions creates a chain of rings which runs parallel to [2-10]. C—H...π and π–π [centroid–centroid distance = 3.8654 (10) Å] interactions are also observed.

In the title compound, C15H10O2, a 3-phenyl derivative of the coumarin (also known as 2H-chromen-2-one or 2H-1-benzopyran-2-one) scaffold, the Cp—Cp—Cc—Cc torsion angle between the coumarin (c) ring system and the phenyl (p) ring is −47.6 (2)°.

Adverse drug events (ADEs) detection and assessment is at the center of pharmacovigilance. Data mining of systems, such as FDA's Adverse Event Reporting System (AERS) and more recently, Electronic Health Records (EHRs), can aid in the automatic detection and analysis of ADEs. Although different data mining approaches have been shown to be valuable, it is still crucial to improve the quality of the generated signals.To leverage structural similarity by developing molecular fingerprint-based models (MFBMs) to strengthen ADE signals generated from EHR data.A reference standard of drugs known to be causally associated with the adverse event pancreatitis was used to create a MFBM. Electronic Health Records (EHRs) from the New York Presbyterian Hospital were mined to generate structured data. Disproportionality Analysis (DPA) was applied to the data, and 278 possible signals related to the ADE pancreatitis were detected. Candidate drugs associated with these signals were then assessed using the MFBM to find the most promising candidates based on structural similarity.The use of MFBM as a means to strengthen or prioritize signals generated from the EHR significantly improved the detection accuracy of ADEs related to pancreatitis. MFBM also highlights the etiology of the ADE by identifying structurally similar drugs, which could follow a similar mechanism of action.The method proposed in this paper provides evidence of being a promising adjunct to existing automated ADE detection and analysis approaches.

Se documenta el caso de un paciente de 78 años de edad con antecedentes de haber sido operado de hiperplasia prostática benigna a través de una adenomectomía retropúbica y, después de retirada la sonda uretral, comenzó a tener salida involuntaria de orina en las posiciones de pie y sentado. Después de 6 meses los síntomas se mantuvieron e intensificaron, y múltiples estudios confirmaron una lesión iatrogénica del esfínter externo. Se realizó una transposición perineal de los cuerpos cavernosos y se creó una uretra funcional de aproximadamente 2,5 cm. Se observó mejoría clínica inmediata que inicialmente solucionó por completo la incontinencia urinaria posquirúrgica. A los 4 años de la operación, el paciente presenta solo escaso goteo posmiccional y ligera salida de orina con los grandes esfuerzos, que mejora con tratamiento médico.This is the case of a male patient aged 78 with a history of benign prostatic hyperplasia surgery through a retropubic adenomectomy and after the urethral stent withdrawal he had an involuntary urine output in standing and sitting down positions. After 6 months the symptoms remained and intensified and multiple studies confirmed an iatrogenic lesion of external sphincter. A perineal transposition of cavernous bodies and a approximately 2,5 cm functional urethra was created. There was an immediate clinical improvement that initially solved completely the postsurgical urinary incontinence. At four year after surgery, patient presents only a low postmicturition dripping and slight urine output with great efforts improving the medical treatment.

Se presenta un nuevo caso de un quiste renal complejo que acude a nuestro centro. La paciente tiene 59 años y hace poco tiempo presenta un dolor lumbar izquierdo mantenido, sordo y gravativo; al examen físico se palpa una tumoración en el hipocondrio y flanco izquierdo. Esta entidad no es rara, pero es difícil de diagnosticar pues en múltiples estudios las imágenes complejas indican una posible afectación tumoral maligna y sólo la exploración quirúrgica define el diagnóstico real. Se describen las características de los quistes renales simples y complejos detallando cómo se realiza el diagnóstico imagenológico de estos casos y la conducta que se sigue en dependencia del grado de complejidad del quiste. Se compara la información encontrada en la literatura médica y la experiencia con esta paciente. Se revisa la literatura encontrada sobre el tema y se comenta la problemática en torno al diagnóstico y a las posibilidades terapéuticas.This is the case of a female patient coming to our center presenting with a complex renal cyst. The patient is aged 59 and a short history of a sustained, dull and severe left lumbar pain; at physical examination a hypochondrium tumor in left flank is palpated. This entity is frequent, but is difficult to diagnose since in multiple studies complex images show possible malign tumor affection, and only the surgical exploration defines the true diagnosis. Features of the simple and complex renal cysts with details on performing of imaging diagnosis of these cases and the behavior followed according the complexity degree of cyst. Information present in medical literature is compared with experience of this patient. Literature on this matter is reviewed and problems around the diagnosis and the therapeutical possibilities are discussed.

El caso que presentamos es el de un paciente de 53 años que, al no tratarse adecuadamente una fimosis, presentó un carcinoma epidermoide de pene y fue necesario realizar una amputación total de este órgano. Es sabido que en la actualidad ese tipo de enfermedad es prevenible y que su aparición se debe a una higiene genital inadecuada relacionada con la presencia de fimosis o prepucio redundanteThe case of a 53 years-old patient, who did not look for adequate treatment for phymosis and developed epidermoid carcinoma of the penis leading to the total amputation of this organ, was presented in this paper. It is known that this type of disease is preventable at present and that it occurs due to phymosis or redundant foreskin-related poor genital hygiene

Presentamos un nuevo caso de quiste multilocular del riñón en el adulto. Esta entidad es sumamente rara y se plantean varias hipótesis sobre su origen. El riñón no tiene configuración reniforme: típicamente el riñón tiene la apariencia de un «racimo de uvas», sin estroma entre los quistes. El tamaño renal es muy variable, pero en ocasiones llega a ser una gran masa que ocupa la mayor parte del abdomen. Se plantea que la diferencia entre esta entidad benigna y los tumores renales intraquíticos solo se puede establecer mediante estudios minuciosos de la pieza anatómica. Se revisa la literatura encontrada sobre el tema y se comenta la problemática en torno al diagnóstico y a las posibilidades terapéuticas

El progreso de la biología y de la medicina en los últimos 20 años ha permitido avanzar en el conocimiento de la fisiopatología, morfología, sintomatología e incluso de nuevas alternativas terapéuticas en los pacientes con hiperplasia prostática benigna (HPB). Se llevó a cabo la presente investigación con el objetivo de evaluar los pacientes que asisten a nuestra consulta y que presentaban HPB a la luz de los nuevos criterios clínico-terapéuticos, e identificar la correlación existente entre estos criterios en dichos pacientes. Se realizó un estudio descriptivo de 56 pacientes con edades comprendidas entre los 50 y los 80 años de edad. A todos los casos se les llenó una encuesta donde se recogieron los síntomas urinarios, el examen físico, el resultado de la uroflujometría y la medición del residuo vesical. Los datos recogidos fueron analizados por métodos paramétricos y los resultados fueron llevados a tablas para una mejor comprensión de éstos. El 66,6 % de los pacientes que tenían un tacto rectal normal presentaban un flujo máximo obstructivo importante y el 50 % de los casos con próstata al tacto grado III tenían flujo no obstructivo. Del total de pacientes con flujo máximo por debajo de 10 mL/s, el 89,2 % tenía un residuo importante. El examen físico es útil para verificar la benignidad del proceso, pero el crecimiento de la glándula a través de la palpación digital no es proporcional al grado de obstrucción; que los síntomas obstructivos e irritativos aparecen con mayor frecuencia en los pacientes con un flujo urinario máximo menor de 10mL/seg. y que la medición del residuo vesical por ultrasonido abdominal nos es muy necesario para completar el estudio de estos pacientesThe progress of biology and medicine in the last years has allowed to advance in the knowldege of physiopathology, morphology, symptomatology and even of new therapeutic alternatives in patients with bening prostatic hyperplasia (BPH). The present research was carried out aimed at evaluating those patients visiting our office and who presented BPH to the light of the new clinicotherapeutic crtieria, and at identifying the correlation existing among these criteria in such patients. A descriptive study of 56 patients aged 50-80 was conducted. All the patients were surveyed and data on the urinary sytem, the physical examination, the result of the uroflowmetry and the measurement of the vesical residual were collected. These data were analyzed by parametric methods and the results were shown in tables for their better comprehension. 66.6 % of the patients with normal rectal touch had an important maximum obstructive flow and 50 % of the cases with degree III prostate to the touch had nonobstructive flow. Of the total of patients with maximum flow under 10 mL/sec, 89.2 % had an important residual. It was concluded that the physical examination is useful to verify the benignancy of the process, that the growth of the gland through digital palpation is not proportional with the obstruction degree, that the obstructive and irritative symptoms appear more frequently in patients with a maximum urinary flow under 10 mL/sec and that the measurement of the vesical residual by abdominal ultrasound is very necessary to complete the study of these patients

Se realizó un estudio para valorar la utilidad del pesquisaje en el diagnóstico del adenocarcinoma de próstata, en 5 consultorios del médico de la familia, en el municipio Plaza de la Revolución, en el período de 1998 al 2000. El universo del estudio estuvo constituido por 97 varones, todos mayores de 50 años y supuestamente sanos. A todos los pacientes se les realizó una dosificación de antígeno prostático específico (PSA) total y luego tacto rectal. En los casos cuando apareció alguna alteración o signo de sospecha de posible desarrollo de células malignas, se les practicó un mapeo citológico de la glándula prostática a través de la biopsia con aguja fina. Se constató en el estudio que el tacto rectal es un examen que mantiene utilidad para el diagnóstico del adenocarcinoma de próstata, y presentó en la investigación una positividad del 15 %. El PSA total se mostró alterado en 6 casos, y fue positivo de células malignas en los 3 pacientes cuando su valor era superior a 10 ng/mL. Aunque la muestra no fue selectiva, es de señalar la alta incidencia de adenocarcinoma de próstata (4,1 %) que aparece en esta investigación

Se revisaron 98 historias clínicas de pacientes operados de hiperplasia prostática benigna en el Servicio de Urología del Hospital Clinicoquirúrgico Docente "Joaquín Albarrán; por las distintas técnicas quirúrgicas. La terapéutica antimicrobiana con kanamicina se utilizó en 41 de estos casos de forma convencional, en dosis de 10 a 15 mg/kg de peso/24 h durante 7 d y los 57 casos restantes recibieron antibioticoterapia perioperatoria con ceftriaxona, en dosis de 1 g intramuscular en el momento de la inducción anestésica y 1 g intramuscular 1 h antes de la remoción del catéter uretral. Se hizo un estudio comparativo de los resultados del uso de ambos métodos profilácticos, donde se demostró el enorme beneficio, desde el punto de vista de los costos, de la ceftriaxona perioperatoria, pues implica una mayor eficacia del medicamento con menores costos hospitalarios