Synthesis and Biological Studies of (+)-Liquiditerpenoic Acid A (Abietopinoic Acid) and Representative Analogues: SAR Studies

[EN] The first semisynthesis and biological profiling of the new abietane diterpenoid (+)-liquiditerpenoic acid A (abietopinoic acid) (7) along with several analogues are reported. The compounds were obtained from readily available methyl dehydroabietate (8), which was derived from (-)-abietic acid (1). Biological comparison was conducted according to the different functional groups, leading to some basic structure-activity relationships (SAR). In particular, the ferruginol and sugiol analogues 7 and 10-16 were characterized by the presence of an acetylated phenolic moiety, an oxidized C-7 as a carbonyl, and a different functional group at C-18 (methoxycarbonyl, carboxylic acid, and hydroxymethyl). The biological properties of these compounds were investigated against a panel of six representative human tumor solid cells (A549, HBL-100, HeLa, SWI573, T-47D, and WiDr), five leukemia cellular models (NALM-06, KOPN-8, SUP-B15, UoCB1, and BCR-ABL), and four Leishmania species (L. infantum, L. donovani, L. amazonensis, and L. guyanensis). A molecular docking study pointed out some targets in these Leishmania species. In addition, the ability of the compounds to modulate GABA(A) receptors (alpha(1)beta(2)gamma(2s)) is also reported. The combined findings indicate that these abietane diterpenoids offer a source of novel bioactive molecules with promising pharmacological properties from cheap chiral-pool building blocks.Financial support by the Spanish Government [Consejo Superior de Investigaciones Cientificas (2016801008)] is gratefully acknowledged. M.S. thanks the support by the doctoral program "Molecular Drug Targets" (Austrian Science Fund FWF W 1232). F.R thanks the American Lebanese Syrian Associated Charities (ALSAC). M.A.D.-A. thanks the Santander Bank for the support for her project in consolidable groups of CEU-UCH.Hamulic, D.; Stadler, M.; Hering, S.; Padron, JM.; Bassett, R.; Rivas, F.; Loza-Mejia, M.... (2019). Synthesis and Biological Studies of (+)-Liquiditerpenoic Acid A (Abietopinoic Acid) and Representative Analogues: SAR Studies. Journal of Natural Products. 82(4):823-831. https://doi.org/10.1021/acs.jnatprod.8b00884S82383182

Ejercicios para mejorar la anticipación en la captura de rebotes ofensivos en el baloncesto de la extensión morona santiago (Original)

To solve the inadequacies in the learning process that are manifested in the children in the capacity of anticipation in the offensive rebound in the masculine team of the Polytechnical Superior School of Chimborazo extension Morona Santiago. The universe of work consisted of 16 athletes. This research was carried out with the objective of preparing a proposal of exercises to improve the anticipation in the capture of offensive rebounds, it is based on the knowledge of the concept of orientation in the rebound area and the place where the failed shots are aimed at and long distance, the performance of the offensive rebound was evaluated starting from dimensions and indicators associated with it such as (skill, physical preparation, anticipation and spatial orientation). An adjustment work was proposed, making successive scores and experiences of the player in situations of games, as well as a perceptive work, developing the selective attention of the stimuli of the environment. What has been learned in this way led to an increase in knowledge in anticipation of the difficulties, reducing the time to make decisions about them and reaching a high level in the capture of offensive rebounds.Para dar solución a las insuficiencias en el proceso de aprendizaje que se manifiestan en los niños en la capacidad de anticipación en el rebote ofensivo en el equipo masculino de la Escuela Superior Politécnica de Chimborazo extensión Morona Santiago. El universo de trabajo estuvo constituido por 16 atletas. Esta investigación se realizó con el objetivo de elaborar una propuesta de ejercicios para mejorar la anticipación en la captura de rebotes ofensivos, la misma se basa en el conocimiento del concepto de orientación en área del rebote y el lugar donde se dirigen los tiros fallidos a media y larga distancia, se valoró el desempeño del rebote ofensivo partiendo de dimensiones e indicadores asociados a este como (habilidad, preparación física, anticipación y orientación espacial). Se propuso un trabajo de ajuste, realizando sucesivos tanteos y vivencias del jugador en situaciones de juegos, así como un trabajo perceptivo, desarrollando la atención selectiva de los estímulos del entorno. Lo aprendido por este camino propició un aumento del conocimiento en la anticipación de las dificultades reduciendo el tiempo para tomar decisiones sobre ellas y alcanzar un alto nivel en la captura de rebotes ofensivos

α-Glucosidase inhibitors from a mangrove associated fungus, Zasmidium sp. strain EM5-10

Abstract Background Mangroves plants and their endophytes represent a natural source of novel and bioactive compounds. In our ongoing research on mangrove endophytes from the Panamanian Pacific Coast, we have identified several bioactive endophytic fungi. From these organisms, an isolate belonging to the genus Zasmidium (Mycosphaerellaceae) showed 91.3% of inhibition against α-glucosidase enzyme in vitro. Results Zasmidium sp. strain EM5-10 was isolated from mature leaves of Laguncularia racemosa, and its crude extract showed good inhibition against α-glucosidase enzyme (91.3% of inhibition). Bioassay-guided fractionation of the crude extract led to obtaining two active fractions: L (tripalmitin) and M (Fungal Tryglicerides Mixture). Tripalmitin (3.75 µM) showed better inhibitory activity than acarbose (positive control, IC50 217.71 µM). Kinetic analysis established that tripalmitin acted as a mixed inhibitor. Molecular docking and molecular dynamics simulations predicted that tripalmitin binds at the same site as acarbose and also to an allosteric site in the human intestinal α-glucosidase (PDB: 3TOP). Conclusions Zasmidium sp. strain EM5-10 represents a new source of bioactive substances that could possess beneficial properties for human health