Bispyrrolidinoindoline Epi(poly)thiodioxopiperazines (BPI-ETPs) and simplified mimetics: structural characterization, bioactivities, and total synthesis

Within the 2,5-dioxopiperazine-containing natural products generated by “head-to-tail” cyclization of peptides, those derived from tryptophan allow further structural diversification due to the rich chemical reactivity of the indole heterocycle, which can generate tetracyclic fragments of hexahydropyrrolo[2,3-b]indole or pyrrolidinoindoline skeleton fused to the 2,5-dioxopiperazine. Even more complex are the dimeric bispyrrolidinoindoline epi(poly)thiodioxopiperazines (BPI-ETPs), since they feature transannular (poly)sulfide bridges connecting C3 and C6 of their 2,5-dioxopiperazine rings. Homo- and heterodimers composed of diastereomeric epi(poly)thiodioxopiperazines increase the complexity of the family. Furthermore, putative biogenetically generated downstream metabolites with C11 and C11’-hydroxylated cores, as well as deoxygenated and/or oxidized side chain counterparts, have also been described. The isolation of these complex polycyclic tryptophan-derived alkaloids from the classical sources, their structural characterization, the description of the relevant biological activities and putative biogenetic routes, and the synthetic efforts to generate and confirm their structures and also to prepare and further evaluate structurally simple analogs will be reported.Xunta de Galicia | Ref. GRC ED431C 2021/045Ministerio de Economía | Ref. PID2019-107855RB-I00Xunta de Galicia | Ref. ED-431G/02-FEDE

Assessing the individual acquisition of teamwork competence by exploring students’ instant messaging tools use: the WhatsApp case study

[En] Nowadays, working in groups is very usual and popular in most professional environments. Thus, students, as potential workers, need to acquire teamwork competence in their educational institutions. However, when the students are working in groups, it is easy assessing their final result but not so much evaluating how each of them, individually, is developing teamwork competence. In this sense, there are several methodologies, and those with better results are the ones that explore students’ interactions in learning platforms when developing the activity/project. Taking into account the latter, students’ interactions do not only happen in a learning platform but also using other tools such as instant messaging tools. This paper explores the possibility to assess the use of instant messaging tools for the acquisition of teamwork competence, and specifically, it presents a case study about the use of WhatsApp. From the results, we can conclude that the students prefer to use instant messaging tools in teamwork activities than other interaction tools as forums; and that the employment of those tools has a positive impact in students’ grades.SIRoboSTEA

Synthetic studies on alotamide A: construction of N‐demethylalotamide A

Financiado para publicación en acceso aberto: Universidade de Vigo/CISUGSeveral approaches to the synthesis of cyclodepsipeptide natural product alotamide A are described, eventually affording a very advanced N-demethylated analogue of the targeted natural product. The difficulties found in our endeavors on the synthesis of alotamide A have allowed us to gather some valuable information regarding the most convenient synthetic step for each key transformation. The intramolecular Csp2−Csp2 Stille cross-coupling and the macrolactam formation were found to be reliable protocols for the final construction of the alotamide A skeleton.Agencia Estatal de Investigación | Ref. PID2019-107855RB−I00Xunta de Galicia | Ref. ED431 C 2021/45Xunta de Galicia | Ref. ED431G/0

Stereoselective Synthesis of Bisfuranoxide (Aurochrome, Auroxanthin) and Monofuranoxide (Equinenone 5′,8′-Epoxide) Carotenoids by Double Horner–Wadsworth–Emmons Reaction

Financiado para publicación en acceso aberto: Universidade de Vigo/CISUGThe stereoselective synthesis of C40-all-trans-carotenoids with the formal hexahydrobenzofuran skeletons aurochrome, auroxanthin, and equinenone-5′,8′-epoxide is reported. The synthesis is based on a one-pot or stepwise double Horner–Wadsworth–Emmons (HWE) reaction of a terminal enantiopure C15-5,6-epoxycyclohexadienylphosphonate and a central C10-trienedial. The ring expansion of the epoxycyclohexadienylphosphonate, generated by a Stille cross-coupling reaction, to the hexahydrobenzofuran skeleton was promoted by the reaction conditions of the HWE reaction prior to double-bond formation.Xunta de Galicia | Ref. ED-431G/02-FEDERXunta de Galicia | Ref. GRC ED431C 2017/61Agencia Estatal de Investigación | Ref. PID2019-107855RB-I0

Total synthesis of homo- and heterodimeric bispyrrolidinoindoline dioxopiperazine natural products

Total synthesis and structural confirmation of homo- and heterodimeric bispyrrolidinoindoline dioxopiperazine alkaloids isolated from fungi and bacteria, namely, ditryptoleucine A, ditryptoleucine B (11), the N,N′-bis-demethylated analogue (+)-12, (−)-dibrevianamide F (13), (−)-SF-5280-451 (14), tetratryptomycin A (15), (−)-tryprophenaline (17), and (−)-SF-5280-415 (18), has been carried out starting from the corresponding bispyrrolidinoindolines derived from tryptophan. Our efforts to synthesize all possible diastereomers of the natural ditryptoleucine isolates uncovered structural factors that determine the rate and efficiency of dioxopiperazine ring formation, leading in some cases to mixtures of diastereomers by concomitant epimerization, to the formation of their putative monomeric dioxopiperazine dipeptide biogenetic precursors, and to the alternative formation of a dimer with a fused 1,3,5-triazepan-6-one heterocycle.Financiado para publicación en acceso aberto: Universidade de Vigo/CISUGMinisterio de Economía y Competitividad | Ref. SAF2016-77620-RXunta de Galicia | Ref. ED-431G/02 INBIOMED-FEDERXunta de Galicia | Ref. ED431C 2017/6

Predicting academic success through students’ interaction with Version Control Systems

[EN] Version Control Systems are commonly used by Information and communication technology professionals. These systems allow monitoring programmers activity working in a project. Thus, Version Control Systems are also used by educational institutions. The aim of thiswork is to evaluate if the academic success of students may be predicted by monitoring their interaction with a Version Control System. In order to do so, we have built a Machine Learning modelwhich predicts student results in a specific practical assignment of the Operating Systems Extension subject, from the second course of the degree in Computer Science of the University of León, through their interaction with a Git repository. To build the model, several classifiers and predictors have been evaluated. In order to do so, we have developed Model Evaluator (MoEv), a tool to evaluate Machine Learning models in order to get the most suitable for a specific problem. Prior to the model development, a feature selection from input data is done. The resulting model has been trained using results from 2016– 2017 course and later validated using results from 2017– 2018 course. Results conclude that the model predicts students’ success with a success high percentage.S

Epigenetic modulator UVI5008 inhibits MRSA by interfering with bacterial gyrase

The impact of multi-drug resistant bacterial strains on human health is reaching worrisome levels. Over 2 million people are infected by resistant bacteria, and more than 700,000 people die each year because of the continuous spread of resistant strains. The development of new antibiotics and the prudent use of existing ones to prolong their lifespan require a constant effort by drug industries and healthcare workers. The re-purposing of existing drugs for use as antimicrobial agents would streamline the development of new antibacterial strategies. As part of this effort, we screened a panel of drugs previously characterized to be epigenetic modulators/pro-apoptotic/differentiative drugs. We selected a few compounds that alter Gram-positive growth. Among these, UVI5008, a derivative of the natural compound psammaplin A (Psa_A), was identified. The interaction of Psa_A with the DNA gyrase enzyme has been shown, and here, we hypothesized and confirmed the gyrase-specific activity by biochemical assays. UVI5008 exhibited growth inhibition activity against Staphylococcus aureus via structural modification of the cell wall, which was observed by SEM electron microscopy. Based on our findings, we propose UVI5008 as an alternative antibacterial compound against methicillin-resistant (Met.R) S. aureus strainsMinisterio de Economía | Ref. SAF2016-77620-R-FEDERXunta de Galicia | Ref. ED431C 29017/61Xunta de Galicia | Ref. ED-431G/02-FEDERProgramma di Ricerca Scientifica di Rilevante Interesse Nazionale | Ref. PRIN-20152TE5PK_00

Evaluación cuantitativa de la adquisición de la competencia de trabajo en equipo mediante la metodología CTMTC

Mención honorífica 2017[ES] La adquisición por los estudiantes de la competencia de trabajo en equipo (TE de aquí en adelante) se considera un aspecto fundamental en la formación de los individuos que ha llevado a su inclusión en los programas de la mayor parte de los grados de las universidades españolas. Esto se debe principalmente a dos razones: 1) El aprendizaje del estudiante se ve mejorado cuando este se lleva a cabo en grupo; de hecho compartir y debatir información en grupo facilita que los estudiantes construyan modelos mentales y por tanto conocimiento conjunto (Leidner & Jarvenpaa, 1995; Vogel, Davison, & Shroff, 2001); y 2) La competencia TE es algo muy apreciado en el ámbito laboral, ya que las instituciones buscan cooperación entre sus miembros para conseguir objetivos comunes (Iglesias-Pradas, Ruiz-de-Azcárate, & Agudo-Peregrina, 2015). Estas razones han hecho que la adquisición de la competencia TE sea algo especialmente tenido en cuenta en contextos educativos, como demuestra que sea una evidencia considerada por programas de evaluación de la calidad como ABET (Accreditation Board for Engineering and Technology) (ABET, 2013) o por la ANECA en sus programas de acreditación del profesorado (ANECA, 2015)

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Epigenetic polypharmacology: from combination therapy to multitargeted drugs

The modern drug discovery process has largely focused its attention in the so-called magic bullets, single chemical entities that exhibit high selectivity and potency for a particular target. This approach was based on the assumption that the deregulation of a protein was causally linked to a disease state, and the pharmacological intervention through inhibition of the deregulated target was able to restore normal cell function. However, the use of cocktails or multicomponent drugs to address several targets simultaneously is also popular to treat multifactorial diseases such as cancer and neurological disorders. We review the state of the art with such combinations that have an epigenetic target as one of their mechanisms of action. Epigenetic drug discovery is a rapidly advancing field, and drugs targeting epigenetic enzymes are in the clinic for the treatment of hematological cancers. Approved and experimental epigenetic drugs are undergoing clinical trials in combination with other therapeutic agents via fused or linked pharmacophores in order to benefit from synergistic effects of polypharmacology. In addition, ligands are being discovered which, as single chemical entities, are able to modulate multiple epigenetic targets simultaneously (multitarget epigenetic drugs). These multiple ligands should in principle have a lower risk of drug-drug interactions and drug resistance compared to cocktails or multicomponent drugs. This new generation may rival the so-called magic bullets in the treatment of diseases that arise as a consequence of the deregulation of multiple signaling pathways provided the challenge of optimization of the activities shown by the pharmacophores with the different targets is addressed.Ministerio de Economía y Competitividad | Ref. SAF2013-48397-RXunta de Galicia | Ref. 2013/00