Leishmanicidal Activity of Nine Novel Flavonoids from Delphinium staphisagria

Objectives. To evaluate the in vitro leishmanicidal activity of nine flavonoid derivatives from Delphinium staphisagria against L. infantum and L. braziliensis. Design and Methods. The in vitro activity of compounds 1–9 was assayed on extracellular promastigote and axenic amastigote forms and on intracellular amastigote forms of the parasites. Infectivity and cytotoxicity tests were carried on J774.2 macrophage cells using Glucantime as the reference drug. The mechanisms of action were analysed performing metabolite excretion and transmission electronic microscope ultrastructural alteration studies. Results. Nine flavonoids showed leishmanicidal activity against promastigote as well as amastigote forms of Leishmania infantum and L. braziliensis. These compounds were nontoxic to mammalian cells and were effective at similar concentrations up to or lower than that of the reference drug (Glucantime). The results showed that 2″-acetylpetiolaroside (compound 8) was clearly the most active. Conclusion. This study has demonstrated that flavonoid derivatives are active against L. infantum and L. braziliensis

Effective Tetradentate Compound Complexes against Leishmania spp. that Act on Critical Enzymatic Pathways of These Parasites

The spectrum and efficacy of available antileishmanial drugs is limited. In the present work we evaluated in vitro the antiproliferative activity of 11 compounds based on tetradentate polyamines compounds against three Leishmania species (L. braziliensis, L. donovani and L. infantum) and the possible mechanism of action. We identified six compounds (3, 5, 6, 7, 8 and 10) effective against all three Leishmania spp both on extracellular and intracellular forms. These six most active leishmanicidal compounds also prevent the infection of host cells. Nevertheless, only compound 7 is targeted against the Leishmania SOD. Meanwhile, on the glucose metabolism the tested compounds have a species-specific effect on Leishmania spp.: L. braziliensis was affected mainly by 10 and 8, L. donovani by 7, and L. infantum by 5 and 3. Finally, the cellular ultrastructure was mainly damaged by 11 in the three Leishmania spp. studied. These identified antileishmania candidates constitute a good alternative treatment and will be further studied.This research was funded by THE SPANISH MINISTRY OF ECONOMY AND COMPETITIVENESS (MINECO), CONSOLIDER-INGENIO 2010, grant number CDS2010-00065; THE EUROPEAN RESEARCH FOUNDATION, grant number ERC-2009-StG-239910; THE MICINN, grant number CTQ2009-08464; and INNPLANTA, grant number INP-2011-0059-PCT-420000-ACT1

In vitro and in vivo studies of the trypanocidal activity of four terpenoid derivatives against Trypanosoma cruzi.

Four terpenoid derivatives were examined for their activity against Trypanosoma cruzi. Our results show that two compounds were very active in vitro against both extra- and intracellular forms. These compounds, non-toxic for the host cells, are more effective than the reference drug benznidazole. The capacity to infect cells was negatively affected and the number of amastigotes and trypomastigotes was reduced. A wide range of ultrastructural alterations was found in the epimastigote forms treated with these compounds. Some metabolic changes occurred presumably at the level of succinate and acetate production, perhaps caused by the disturbance of the enzymes involved in sugar metabolism inside the mitochondria. In vivo results were consistent with those observed in vitro. The parasitic load was significantly lower than in the control assay with benznidazole. The effects of these products showed the reduction of the anti-T. cruzi antibodies level during the chronic stage

Competencias de liderazgo en el proceso de enseñanza aprendizaje de los administradores de empresas de la Universidad de Manizales

The article refers to the competencies of business practice, the basic competencies of managerial leadership and the specific ones of leadership; essential in the formative process of business management at the Universidad de Manizales, taking into account the reflections and perspectives of the Tuning Latin America Project period 2011-2013 (2021); as well as the professional and occupational profile proposed by the program and other competencies that are required to provide solutions to real situations in organizations. For this purpose, a research with a quantitative approach with an exploratory and correlational scope was carried out, through the statistical method of Principal Component Analysis, the survey was applied to graduates (132) and students (81) as an instrument of data collection. It is concluded that the basic competencies of managerial leadership are considered crucial in the training processes of the population under study, with which they are able to demonstrate in their actions: integrity, ease of communication, strategic vision, focus on obtaining results, decision making, negotiation skills, team building and development, perseverance and time management to face the challenges in their professional future.   Key words: competencies, leadership competencies, teaching-learning, business managers, principal component analysis.El artículo hace referencia a las competencias de la práctica empresarial, las  básicas del liderazgo gerencial y las específicas de liderazgo; esenciales en el proceso formativo de los administradores de empresas de la Universidad de Manizales,  teniendo en cuenta tanto las reflexiones y perspectivas del Proyecto Tuning América Latina periodo 2011-2013 (2021); como el perfil profesional y ocupacional  propuesto por el programa y demás competencias que se requieren para dar solución a situaciones reales en las organizaciones. Para ello, se realizó una investigación con enfoque cuantitativo con un alcance exploratorio y correlacional, a través del método estadístico de Análisis de Componentes Principales, se aplicó la encuesta a los egresados (132) y estudiantes (81) como instrumento de recolección de datos. Se concluye que las competencias básicas de liderazgo gerencial son consideradas como cruciales en los procesos de formación de la población objeto de estudio, con las cuales están en capacidad de demostrar en su actuar: integridad, facilidad de comunicación, visión estratégica, enfoque hacia la obtención de resultados, toma de decisiones, habilidades de negociación, creación y desarrollo de equipos, perseverancia y administración del tiempo para afrontar los retos en su futuro profesional.   Palabras clave: competencias, competencias de liderazgo, enseñanza-aprendizaje, administradores de empresas, análisis de componentes principales

Responsabilidad Social Pública para contribuir a la consolidación de los Objetivos del Desarrollo Sostenible

The purpose of article is investigates the literary corpus on the role of Public Social Responsibility (PSR) in contributing to sustainable development; therefore, the paper discusses that it is necessary to transform into a united approach all levels of society and its organizations of different kinds to achieve from a socially responsible public administration the implementation of Agenda 2030, in the action of strategies for Member States aim to contribute to the consolidation of the Sustainable Development Goals (SDGs). The methodological design is based on a qualitative approach with a hermeneutic and comprehensive scope, to carry out an observational and retrospective analysis on a database containing 44 publications in English published between 2001 and 2020 (February), which provides a qualitative view of the academic literature in this field. In terms of findings and results, the literature review identified that research on PSR is linked to the concept of sustainability and focuses on the importance of tangible actions, thus establishing a relationship from the primary attributes that promote socially responsible management of public administration of the entities of the States Parties, towards the contribution of SDGs in an inclusive, sustainable and resilient manner, that constitute a universal commitment. In summary, this paper contributes to the literature on PSR as a driver for SDGs, providing a systematic review of the literature on these topics from the perspective of socially responsible management for sustainable development.El propósito del artículo es investigar el corpus literario sobre el papel de la Responsabilidad Social Pública (RSP) para contribuir desarrollo sostenible; discute la necesidad de la transformación a un enfoque unido de todos los niveles de la sociedad y sus organizaciones desde diferentes índoles para lograr desde una administración pública socialmente responsable la implementación de la Agenda 2030, en la acción de estrategias para que los Estados Miembros le apunten a aportar a la consolidación de los Objetivos del Desarrollo Sostenible (ODS). El diseño metodológico, se trabajó desde un enfoque cualitativo con un alcance hermenéutico-comprensivo, realizando un análisis observacional y retrospectivo sobre una base de datos que contiene 44 publicaciones en idioma inglés publicados entre 2001 y 2020 (febrero). Como hallazgos y resultados, el análisis bibliográfico identificó que la investigación sobre la RSP está vinculada al concepto de la sostenibilidad y centrada en la importancia de las acciones tangibles, por lo cual se logró establecer una relación desde los atributos primordiales que fomentan la gestión socialmente responsable de la administración pública de las entidades de los Estados Parte, hacia la contribución de los ODS de una manera inclusiva, sostenible y resiliente, lo cual constituye un compromiso universal. En síntesis, este documento contribuye a la literatura sobre RSP como un conductor para los ODS, proporcionando una revisión sistemática de la literatura sobre estos temas bajo la perspectiva de la gestión socialmente responsable para un desarrollo sostenible

In vitro evaluation of new terpenoid derivatives against Leishmania infantum and Leishmania braziliensis.

The activity of five (1-5) abietane phenol derivatives against Leishmania infantum and Leishmania braziliensis was studied using promastigotes and axenic and intracellular amastigotes. Infectivity and cytotoxicity tests were performed with J774.2 macrophage cells using Glucantime as a reference drug. The mechanisms of action were analysed by performing metabolite excretion and transmission electron microscopy ultrastructural studies. Compounds 1-5 were more active and less toxic than Glucantime. The infection rates and mean number of parasites per cell observed in amastigote experiments showed that derivatives 2, 4 and 5 were the most effective against both L. infantum and L. braziliensis. The ultrastructural changes observed in the treated promastigote forms confirmed that the greatest cell damage was caused by the most active compound (4). Only compound 5 caused changes in the nature and amounts of catabolites excreted by the parasites, as measured by ¹H nuclear magnetic resonance spectroscopy. All of the assayed compounds were active against the two Leishmania species in vitro and were less toxic in mammalian cells than the reference drug

In vivo trypanosomicidal activity of imidazole- or pyrazole-based benzo[ g ]phthalazine derivatives against acute and chronic phases of chagas disease

The in vivo trypanosomicidal activity of the imidazole-based benzo[g]phthalazine derivatives 1−4 and of the new related pyrazole-based compounds 5 and 6 has been studied in both the acute and chronic phases of Chagas disease. As a rule, compounds 1−6 were more active and less toxic than benznidazole in the two stages of the disease, and the monosubstituted derivatives 2, 4, and 6 were more effective than their disubstituted analogs. Feasible mechanisms of action of compounds 1−6 against the parasite have been explored by considering their inhibitory effect on the Fe-SOD enzyme, the nature of the excreted metabolites and the ultrastructural alterations produced. A complementary histopathological analysis has confirmed that the monosubstituted derivatives are less toxic than the reference drug, with the behavior of the imidazole-based compound 4 being especially noteworthy.The authors thank the Santander-Universidad Complutense Research Program (Grant GR58/08-921371-891), the Spanish MEC Project (Grant CGL2008-03687-E/BOS), and the MCINN Projects (CTQ2009-14288-C04-01 and Consolider CSD2010-00065) for financial support

Gallic Acid: A Natural Phenolic Compound Exerting Antitumoral Activities in Colorectal Cancer via Interaction with G-Quadruplexes

Natural phenolic compounds have gained momentum for the prevention and treatment of cancer, but their antitumoral mechanism of action is not yet well understood. In the present study, we screened the antitumoral potential of several phenolic compounds in a cellular model of colorectal cancer (CRC).We selected gallic acid (GA) as a candidate in terms of potency and selectivity and extensively evaluated its biological activity. We report on the role of GA as a ligand of DNA G-quadruplexes (G4s), explaining several of its antitumoral effects, including the transcriptional inhibition of ribosomal and CMYC genes. In addition, GA shared with other established G4 ligands some effects such as cell cycle arrest, nucleolar stress, and induction of DNA damage. We further confirmed the antitumoral and G4-stabilizing properties of GA using a xenograft model of CRC. Finally, we succinctly demonstrate that GA could be explored as a therapeutic agent in a patient cohort with CRC. Our work reveals that GA, a natural bioactive compound present in the diet, affects gene expression by interaction with G4s both in vitro and in vivo and paves the way towards G4s targeting with phenolic compounds.Instituto de Salud Carlos IIIEuropean Commission PI21/00497 AC18/00008Next generation EU, Plan de Recuperacion Transformacion y Resiliencia, Agencia Estatal de Investigacion PLEC2021-008094Ministerio de Ciencia e Innovacion from Government of Spain PID2019-104416RB-I00 PID2020-120481RB-I00Ministerio de Universidades from Government of Spain FPU16/05822 FPU17/05413 FPU20/03952University of Almeria FPI-20110

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p < 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics