Natural products play an invaluable role as a starting point in the drug discovery process, and plants and animals use many interesting biologically active natural products as a chemical defense ...mechanism against predators. Among marine organisms, many nudibranch gastropods are known to derive defensive metabolites from the sponges they eat. Here we investigated the putative sequestration of the toxic compound latrunculin A--a 16-membered macrolide that prevents actin polymerization within cellular processes--which has been identified from sponge sources, by five closely related nudibranch molluscs of the genus Chromodoris. Only latrunculin A was present in the rim of the mantle of these species, where storage reservoirs containing secondary metabolites are located, whilst a variety of secondary metabolites were found in their viscera. The species studied thus selectively accumulate latrunculin A in the part of the mantle that is more exposed to potential predators. This study also demonstrates that latrunculin-containing sponges are not their sole food source. Latrunculin A was found to be several times more potent than other compounds present in these species of nudibranchs when tested by in vitro and in vivo toxicity assays. Anti-feedant assays also indicated that latrunculin A was unpalatable to rock pool shrimps, in a dose-dependent manner. These findings led us to propose that this group of nudibranchs has evolved means both to protect themselves from the toxicity of latrunculin A, and to accumulate this compound in the mantle rim for defensive purposes. The precise mechanism by which the nudibranchs sequester such a potent compound from sponges without disrupting their own key physiological processes is unclear, but this work paves the way for future studies in this direction. Finally, the possible occurrence of both visual and chemosensory Müllerian mimicry in the studied species is discussed.
Cultures of the estuarine fungus Penicillium roseopurpureum (CMB-MF038) yielded a diverse array of polyketides, many of which were related via a highly convergent biosynthetic pathway. In addition to ...revising and assigning structures, and documenting chemical and biological properties, pro-drug cytotoxic properties were attributed to roseopurpurins H (10) and I (11) on the basis of in situ reverse Michael addition to a cytotoxic Michael acceptor (12).
Chemical analysis of a marine-derived fungus, Chaunopycnis sp. (CMB-MF028), isolated from the inner tissue of a pulmonate false limpet Siphonaria sp., collected from rock surfaces in the intertidal ...zone of Moora Park, Shorncliffe, Queensland, yielded the tetramic acid F-14329 (1) and new analogues, chaunolidines A-C (2-4), together with the new pyridinone chaunolidone A (5), and pyridoxatin (6). Structures inclusive of absolute configurations were assigned to 1-6 on the basis of detailed spectroscopic analysis, X-ray crystallography, electronic circular dichroism (ECD), biosynthetic considerations and chemical interconversion. Chaunolidine C (4) exhibits modest Gram-positive antibacterial activity (IC50 5-10 μM), while chaunolidone A (5) is a selective and potent inhibitor (IC50 0.09 μM) of human non-small cell lung carcinoma cells (NCI-H460). Tetramic acids 1-4 form metal chelates with Fe(III), Al(III), Cu(II), Mg(II) and Zn(II).
The stress response is a well-defined physiological function activated frequently by life events. However, sometimes the stress response can be inappropriate, excessive, or prolonged; in which case, ...it can hinder rather than help in coping with the stressor, impair normal functioning, and increase the risk of somatic and mental health disorders. There is a need for a more effective and safe pharmacological treatment that can dampen maladaptive stress responses. The endocannabinoid system is one of the main regulators of the stress response. A basal endocannabinoid tone inhibits the stress response, modulation of this tone permits/curtails an active stress response, and chronic deficiency in the endocannabinoid tone is associated with the pathological complications of chronic stress. Cannabidiol is a safe exogenous cannabinoid enhancer of the endocannabinoid system that could be a useful treatment for stress. There have been seven double-blind placebo controlled clinical trials of CBD for stress on a combined total of 232 participants and one partially controlled study on 120 participants. All showed that CBD was effective in significantly reducing the stress response and was non-inferior to pharmaceutical comparators, when included. The clinical trial results are supported by the established mechanisms of action of CBD (including increased N-arachidonylethanolamine levels) and extensive real-world and preclinical evidence of the effectiveness of CBD for treating stress.
are Gram-positive bacteria that occupy diverse ecological niches including host-associations with animals and plants. Members of this genus are known for their overwhelming repertoire of natural ...products, which has been exploited for almost a century as a source of medicines and agrochemicals. Notwithstanding intense scientific and commercial interest in
natural products, surprisingly little is known of the intra- and/or inter-species ecological roles played by these metabolites. In this report we describe the chemical structures, biological properties, and biosynthetic relationships between natural products produced by
isolated from internal tissues of predatory
snails, collected from the Great Barrier Reef, Australia. Using chromatographic, spectroscopic and bioassays methodology, we demonstrate that
isolated from five different
species produce identical chemical and antifungal profiles - comprising a suite of polycyclic tetramic acid macrolactams (PTMs). To investigate possible ecological (and evolutionary) relationships we used genome analyses to reveal a close taxonomic relationship with other sponge-derived and free-living PTM producing
(i.e.,
). In-depth phylogenomic analysis of PTM biosynthetic gene clusters indicated PTM structure diversity was governed by a small repertoire of genetic elements, including discrete gene acquisition events involving dehydrogenases. Overall, our study shows a
-
ecological relationship that is concomitant with specific PTM chemical profiles. We provide an evolutionary framework to explain this relationship, driven by anti-fungal properties that protect
snails from fungal pathogens.
En la actualidad las compañías de seguros se basan en modelos de respuesta para los siniestros, herramienta que verifica el estado en tiempo real de los contratiempos de sus asegurados, forzando a ...las compañías a mejorar procesos, directrices y atención al cliente. El objetivo de este artículo es establecer pautas y estrategias que ayuden al actual modelo de recepción de siniestros y brindar una pronta respuesta y solución a los mismos, mediante indicadores financieros de los años 2017-2020. Para este propósito se utilizó un enfoque: cuantitativo, descriptivo, explicativo y longitudinal; con ayuda de estados de situación financiera de la Compañía “Seguros Alianza” para sugerir aspectos a perfeccionar, de esta manera sentar un precedente para las diferentes compañías de Seguros; los resultados manifestaron la importancia de una mejora continua en los procesos, renovando su percepción en la sociedad, debido a la capacidad de generar beneficios, reflejados mediante el indicador de liquidez el cual presentó un resultado del 0,18 demostrando que sus activos líquidos cubrieron sus obligaciones a corto plazo, con respecto al indicador de solvencia se obtuvo 1,6 evidenciando la capacidad para satisfacer sus compromisos de pago, en cuanto al Roe refleja un 92,25% para los periodos estudiados, lo que significa que puede cubrir sus pasivos y ser base fundamental para una correcta toma de decisiones por los directivos, como para su análisis de viabilidad de la inversión, por lo cual se propone un modelo estándar para el manejo y respuesta adecuada de los siniestros para las diferentes compañías de seguros.
Chemical profiling of extracts from a mud dauber wasp-associated fungus, Aspergillus sp. (CMB-W031), revealed a remarkably diverse array of secondary metabolites, with many biosynthetic gene clusters ...being transcriptionally responsive to specific culture conditions. Chemical fractionation of a jasmine rice cultivation yielded many known fungal metabolites, including the highly cytotoxic (−)-stephacidin B and an unprecedented nonribosomal peptide synthase derived nitro depsi-tetrapeptide diketopiperazine, waspergillamide A (1). All structures were assigned by detailed spectroscopic analysis and, where appropriate, chemical degradation and Marfey’s analysis.
Chemical analysis of an Australian mud dauber wasp-associated fungus, Talaromyces sp. (CMB-W045), yielded five new coprogen siderophores, talarazines A–E (1–5), together with dimerumic acid (6), ...desferricoprogen (7), and elutherazine B (8). Structures inclusive of absolute configuration were assigned on the basis of detailed spectroscopic analysis and application of the C3 Marfey’s method. We report on the noncytotoxic Fe(III) chelation properties of 1–8 and demonstrate that biosynthesis is regulated by available Fe(III) in culture media. We demonstrate a magnetic nanoparticule approach to extracting high-affinity Fe(III) binding metabolites (i.e., 8) from complex extracts.
Viridicatumtoxins, which belong to a rare class of fungal tetracycline-like mycotoxins, were subjected to comprehensive spectroscopic and chemical analysis, leading to reassignment/assignment of ...absolute configurations and characterization of a remarkably acid-stable antibiotic scaffold. Structure activity relationship studies revealed exceptional growth inhibitory activity against vancomycin-resistant Enterococci (IC50 40 nM), >270-fold more potent than the commercial antibiotic oxytetracycline.
PDF
