Structure, Bioactivity and Analytical Methods for the Determination of Yucca Saponins

Yucca is one of the main sources of steroidal saponins, hence different extracts are commercialized for use as surfactant additives by beverage, animal feed, cosmetics or agricultural products. For a deeper understanding of the potential of the saponins that can be found in this genus, an exhaustive review of the structural characteristics, bioactivities and analytical methods that can be used with these compounds has been carried out, since there are no recent reviews on the matter. Thus, a total of 108 saponins from eight species of the genus Yucca have been described. Out of these, the bioactivity of 68 saponins derived from the isolation of Yucca or other genera has been evaluated. Regarding the evaluation and quality control of the saponins from this genus LC-MS technique is the most often used. Nevertheless, the development of methods for their routine analysis in commercial preparations are needed. Moreover, most of the studies found in the literature have been carried out on Y. schidigera extract, since is the most often used for commercial purposes. Only eight of the 50 species that belong to this genus have been studied, which clearly indicates that the identification of saponins present in Yucca genus is still an unresolved question.This work was financially supported by the 'Ministerio de Economia y Competitividad' (Project AGL2017-88083-R), Spain

Dereplication of Bioactive Spirostane Saponins from Agave macroacantha

A dereplication strategy using UPLC-QTOF/MSE, the HMAI method, and NMR spectroscopy led to the identification of five main steroidal saponins (1-5), including three previously unknown compounds named macroacanthosides A-C (3-5), in a bioactive fraction of Agave macroacantha. The major saponins were isolated, and some of them together with the saponin-rich fraction were then evaluated for phytotoxicity on a standard target species, Lactuca sativa. The inhibition values exhibited by the pure compounds were confirmed to be in agreement with the phytotoxicity of the saponin-rich fraction, which suggests that the saponin fraction could be applied successfully as an agrochemical without undergoing any further costly and/or time-consuming purification processes. The NMR data of the pure compounds as well as of those corresponding to the same compounds in the fraction were comparable, which indicated that the main saponins could be identified by means of this replication workflow and that no standards are required

Agave Steroidal Saponins as Potential Bioherbicides

Agave saponins are a valuable resource for the prospective development of new forms of agrochemicals. The extraction method was optimized and applied to 17 Agave species. Thirteen saponin fractions (SFs) were assayed on wheat etiolated coleoptiles, and analysed using UPLC-QTOFMSE, NMR spectroscopy and the HMBC method for aglycone identification (HMAI). Six SFs were assayed on standard target species (STS) and weeds. The new extraction method reduces costs to obtain SFs with the same activity. The tested SFs assayed on etiolated wheat coleoptiles that belong to the subgenus Agave were among those with the highest activity levels. The combination of HMAI together with UPLC-MS allowed the identification of 20 aglycones in the SFs, and no isolation or hydrolysis of the saponins was required. A Principal Component Analysis (PCA) showed that for the active SFs the structural key would be the length of their sugar chain. The presence of a carbonyl group at C-12 implied an enhancement in phytotoxic activity. Six SFs were assayed on seeds, and no activity on Solanum lycopersicum (tomato) was observed; however, good activity profiles were obtained on weed E. crus-galli (IC50 < 80 ppm), better than the commercial herbicide Logran®. These findings represent a possible lead for the development of natural herbicides through the use of saponins of subgenus Agave species

An Overview of the Chemical Characteristics, Bioactivity and Achievements Regarding the Therapeutic Usage of Acetogenins from Annona cherimola Mill.

Annona cherimola Mill., or the custard apple, is one of the species belonging to the Annonaceae family, is widely used in traditional medicine, and has been reported to be a valuable source of bioactive compounds. A unique class of secondary metabolites derived from this family are Annonaceous acetogenins, lipophilic polyketides considered to be amongst the most potent antitumor compounds. This review provides an overview of the chemical diversity, isolation procedures, bioactivity, modes of application and synthetic derivatives of acetogenins from A. cherimola Mill.This work was financially supported by the 'Ministerio de Economia y Competitividad' (Project AGL2017-88083-R), Spain. F.J.R.M. thanks Universidad de Cadiz for predoctoral support under grant 2018-009/PU/EPIF-FPI-CT/CP

On the formulation of disulfide herbicides based on aminophenoxazinones: polymeric nanoparticle formulation and cyclodextrin complexation to combat crop yield losses

BackgroundThe resistance of weeds to herbicides is a significant issue in ensuring future food supply. Specific examples are Plantago lanceolata, Portulaca oleracea and Lolium rigidum, which mainly infect rice, wheat, barley and pastures, and cause high yield losses every year. In this regard, natural products and their mimics have provided new hope as a result of their different modes-of-action, activity at low concentrations and reduced pollution effects relative to conventional herbicides. However, the poor water solubility and physicochemical properties of these compounds limit their broad application. These problems can be addressed by formulation techniques, and encapsulation appears to be of great interest. ResultsDisulfide herbicides inspired by aminophenoxazinones have been formulated with 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD), gamma-CD and polymeric nanoparticles (NPs). In silico studies were employed to identify which complexes would be generated and complex formation was confirmed by nuclear magnetic resonance spectroscopy. Solubility diagrams were generated to assess any improvement in water solubility, which was enhanced 2-13-fold. Scanning electron microscopy and energy-dispersive X-ray spectra confirmed the success of the formulation process for the nanoparticles. Formulated compounds were evaluated in an in vitro wheat coleoptile bioassay, with almost 100% elongation inhibition achieved using only water for the bioassay. Specific in vitro testing on weed phytotoxicity showed that the application of core/shell NPs is highly effective in the fight against P. lanceolata seed germination. ConclusionsThe formulation of disulfide herbicides with CD complexes and NPs led to an enhancement in water solubility and bioactivity. These systems can be applied in pre-emergent mode against P. lanceolata, using only water to prepare the sample, and they showed better activity than the positive controls. (c) 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industr

In Silico Evaluation of Sesquiterpenes and Benzoxazinoids Phytotoxins against M-pro, RNA Replicase and Spike Protein of SARS-CoV-2 by Molecular Dynamics. Inspired by Nature

In the work described here, a number of sesquiterpenes and benzoxazinoids from natural sources, along with their easily accessible derivatives, were evaluated against the main protease, RNA replicase and spike glycoprotein of SARS-CoV-2 by molecular docking. These natural products and their derivatives have previously shown remarkable antiviral activities. The most relevant compounds were the 4-fluoro derivatives of santamarine, reynosin and 2-amino-3H-phenoxazin-3-one in terms of the docking score. Those compounds fulfill the Lipinski's rule, so they were selected for the analysis by molecular dynamics, and the kinetic stabilities of the complexes were assessed. The addition of the 4-fluorobenzoate fragment to the natural products enhances their potential against all of the proteins tested, and the complex stability after 50 ns validates the inhibition calculated. The derivatives prepared from reynosin and 2-amino-3H-phenoxazin-3-one are able to generate more hydrogen bonds with the M-pro, thus enhancing the stability of the protein-ligand and generating a long-term complex for inhibition. The 4-fluoro derivate of santamarine and reynosin shows to be really active against the spike protein, with the RMSD site fluctuation lower than 1.5 angstrom. Stabilization is mainly achieved by the hydrogen-bond interactions, and the stabilization is improved by the 4-fluorobenzoate fragment being added. Those compounds tested in silico reach as candidates from natural sources to fight this virus, and the results concluded that the addition of the 4-fluorobenzoate fragment to the natural products enhances their inhibition potential against the main protease, RNA replicase and spike protein of SARS-CoV-2

Bio-Guided Isolation of Acetogenins from Annona cherimola Deciduous Leaves: Production of Nanocarriers to Boost the Bioavailability Properties

Annonaceous acetogenins (ACGs) are lipophilic polyketides isolated exclusively from Annonaceae. They are considered to be amongst the most potent antitumor compounds. Nevertheless, their applications are limited by their poor solubility. The isolation of ACGs from Annona cherimola leaves, an agricultural waste, has not been reported to date. Molvizarin (1) cherimolin-1 (2), motrilin (3), annonacin (4) and annonisin (5) are isolated for the first time from A. cherimola deciduous leaves. Annonacin was found to be four- and two-times more potent in tumoral cells (HeLa, 23.6% live cells; IGROV-1, 40.8% live cells for 24 h) than in HEK-293 at 50 mu M (24 h, 87.2% live cells). Supramolecular polymer micelles (SMPMs) were synthesized to encapsulate the major ACG isolated, annonacin, in order to improve its solubility in aqueous media. The bioavailability of this compound was increased by a factor of 13 in a simulated human digestive system when compared with free annonacin and an encapsulation efficiency of 35% was achieved. In addition, the cytotoxic activity of SMPMs that hosted annonacin (100 mu M, 24 h, 5.8% live cells) was increased compared with free annonacin in water (100 mu M, 24 h, 92% live cells). These results highlight the use of by-products of A. cherimola, and their pure compounds, as a promising source of anticancer agents. The use of SMPMs as nanocarriers of ACGs could be an alternative for their application in food field as nutraceutical to enhance the administration and efficacy

Synthesis, antibacterial and antifungal activities of naphthoquinone derivatives: a structure–activity relationship study

The synthesis of 1,4-naphthoquinone derivatives is of great interest since these compounds exhibit strong activity as antimalarial, antibacterial, antifungal and anticancer agents. A series of 50 naphthoquinone derivatives was synthesized and evaluated for antibacterial and antifungal activity against Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis, Staphylococcus aureus, Candida krusei, Candida parapsilosis and Cryptococcus neoformans using the broth microdilution method. The Candida species were the most susceptible microorganisms. Halogen derivatives of 1,4-naphthoquinone presented strong activity, e.g., 2-bromo-5-hydroxy-1,4-naphthoquinone, which exhibited inhibition at an MIC of 16 lg/ mL in S. aureus, and 2-chloro-5,8-dihydroxy-1,4-naphthoquinone, with an MIC of 2 lg/mL in C. krusei. These compounds showed higher activity against fungi, but the antibacterial activities were very low. The study of structure–activity relationships is very important in the search for new antimicrobial drugs due to the limited therapeutic arsenal

Caracterização de cardiopatias congênitas em Manizales, Colômbia, 2010-2016

Congenital heart defects are the third cause of congenital malformations and one of the main causes of mortality in the neonatal period in the world; they originate from alterations in embryonic development. The incidence is variable; in Colombia, it is estimated that they affect 2 to 3% of live newborns. In 2015, 20.8% of children under the age of five affected with congenital heart defects died from these disorders. This is a descriptive and retrospective study. Data of 252 clinical records of patients diagnosed with congenital heart defect between 2010 and 2016 were included, showing that 56% of this population were female. Acyanotic Congenital Heart Diseases predominated (87%). The highest prevalence was patent ductus arteriosus (35.3%). Doppler echocardiography was used in 98.4% of cases; regarding management, 47.2% of patients were in follow-up, this being more common than medical or surgical alternatives. In conclusion patent ductus arteriosus, ventricular septal defect and interatrial septal defect are the most frequent acyanotic heart diseases in the population under study and they are associated with pulmonary hypertension that require higher follow-up. Tetralogy of Fallot was the most common cyanotic congenital heart disease.Las cardiopatías congénitas son la tercera causa de malformaciones congénitas y una de las principales responsables de la mortalidad en periodo neonatal en el mundo; se originan a partir de alteraciones en el desarrollo embrionario. La incidencia es variable; en Colombia, se estima que afectan del 2 al 3 % de los recién nacidos vivos. En 2015, 20,8 % de los niños menores de cinco años afectados con cardiopatías congénitas fallecieron a causa de estas alteraciones. El presente es un estudio descriptivo y retrospectivo. Se incluyeron los datos de 252 historias clínicas de pacientes con diagnóstico de cardiopatía congénita entre los años 2010 y 2016, el 56 % de la población encontrada fue de sexo femenino. Predominaron las cardiopatías congénitas no cianosantes (87 %). La mayor revalencia fue el ductus arterioso permeable (35,3 %). La ecocardiografía Doppler se utilizó en 98,4 % de los casos; con respecto al manejo, el 47,2 % de los pacientes estuvieron en seguimiento, siendo este más común que las alternativas médicas o quirúrgicas. En conclusión, el ductus arterioso permeable, la comunicación interventricular y la comunicación interatrial son las cardiopatías no cianosantes más frecuentes en la población estudiada y se asocian a hipertensión pulmonar que ameritan mayor seguimiento. La tetralogía de Fallot fue la cardiopatía congénita cianosante más común.As cardiopatias congênitas são a terceira causa de malformações congênitas e uma das principais responsáveis pela mortalidade no período neonatal no mundo. São originadas a partir de alterações no desenvolvimento embrionário. A incidência é variável; na Colômbia, é estimado que afetam de 2 a 3 % dos recém-nascidos vivos. Em 2015, 20,8 % das crianças menores de cinco anos afetadas com cardiopatias congênitas faleceram por causa dessas alterações. Este estudo é descritivo e retrospectivo. Foram incluídos dados de 252 prontuários de pacientes com diagnóstico de cardiopatia congênita entre 2010 e 2016, 56 % da população encontrada foi do sexo feminino. Predominaram as cardiopatias congênitas não&nbsp; ianóticas (87 %). A maior persistência foi o ducto arterioso permeável (35,3 %). A ecocardiografia Doppler foi utilizada em 98,4 % dos casos; quanto ao manejo, 47,2 % dos pacientes estiveram em seguimento, o que foi mais comum do que as alternativas médicas ou cirúrgicas. Em conclusão, o ducto arterioso permeável, a comunicação interventricular e a comunicação interatrial são as cardiopatias não cianóticas mais frequentes na população estudada e são associadas com a hipertensão pulmonar que merecem maior seguimento. A tetralogia de Fallot foi a cardiopatia congênita cianótica mais comum

The global distribution and environmental drivers of the soil antibiotic resistome

Background: Little is known about the global distribution and environmental drivers of key microbial functional traits such as antibiotic resistance genes (ARGs). Soils are one of Earth’s largest reservoirs of ARGs, which are integral for soil microbial competition, and have potential implications for plant and human health. Yet, their diversity and global patterns remain poorly described. Here, we analyzed 285 ARGs in soils from 1012 sites across all continents and created the first global atlas with the distributions of topsoil ARGs. Results: We show that ARGs peaked in high latitude cold and boreal forests. Climatic seasonality and mobile genetic elements, associated with the transmission of antibiotic resistance, were also key drivers of their global distribution. Dominant ARGs were mainly related to multidrug resistance genes and efflux pump machineries. We further pinpointed the global hotspots of the diversity and proportions of soil ARGs. Conclusions: Together, our work provides the foundation for a better understanding of the ecology and global distribution of the environmental soil antibiotic resistome.This project received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement 702057 (CLIMIFUN), a Large Research Grant from the British Ecological Society (agreement no. LRA17\1193; MUSGONET), and from the European Research Council (ERC grant agreement no. 647038, BIODESERT). M. D. B. was also supported by a Ramón y Cajal grant (RYC2018-025483-I). M.D-B. also acknowledges support from the Spanish Ministry of Science and Innovation for the I+D+i project PID2020-115813RA-I00 funded by MCIN/AEI/10.13039/501100011033. M.D-B. is also supported by a project of the Fondo Europeo de Desarrollo Regional (FEDER) and the Consejería de Transformación Económica, Industria, Conocimiento y Universidades of the Junta de Andalucía (FEDER Andalucía 2014-2020 Objetivo temático “01 - Refuerzo de la investigación, el desarrollo tecnológico y la innovación”) associated with the research project P20_00879 (ANDABIOMA). FTM acknowledges support from Generalitat Valenciana (CIDEGENT/2018/041). J. Z. H and H. W. H. are financially supported by Australian Research Council (DP210100332). We also thank the project CTM2015-64728-C2-2-R from the Ministry of Science of Spain. C. A. G. and N. E. acknowledge funding by the German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig, funded by the German Research Foundation (FZT 118). TG was financially supported by Slovenian Research Agency (P4-0107, J4-3098 and J4-4547)