Computational predictive approaches present themselves as an attractive alternative in the search for new compounds that may present toxic or growth regulatory activity in Aedes aegypti. Aspergillus species is a producer of secondary metabolites with diverse biological activities. In this study, it was possible to evaluate the pharmacokinetic and toxicological properties in silico, as well as the prediction of the insecticidal biological activities of the juvenile hormone of natural substances produced by the genus Aspergillus. Initially, 187 molecules were cataloged from various species of Aspergillus spp., and only seven molecules of indole alkaloids were found to exhibit a toxic dose 50% (TD50) after conducting toxicity predictions. The molecular dynamic simulation trajectories were utilized to study parameters such as root mean square deviation, root mean square fluctuation, radius of gyration and intermolecular hydrogen bond to understand the behavior and stability of proposed compounds in the binding pocket of the target protein. The N-β-acetyltryptamine molecule showed a binding affinity value of –8.100 ± 0.200 kcal mol-1, which classifies the compound as a potential insecticidal agent against the Aedes aegypti vector. silico Initially 18 spp spp. 50 TD50 TD (TD50 predictions deviation fluctuation protein Nβacetyltryptamine N β acetyltryptamine 8100 8 100 –8.10 0200 0 200 0.20 mol1, mol1 mol 1, 1 mol-1 vector 5 TD5 (TD5 810 10 –8.1 020 20 0.2 mol- (TD 81 –8. 02 2 0. –8 –

Caffeine (CAF) and nicotine (NIC) are emerging contaminants and are among the most consumed substances in the world, making it crucial to monitor these contaminants. In this work, an alternative electrolyte, 2-hydroxyethylammonium acetate (2HEAA) was used for the development of an electroanalytical method for determination and quantification of CAF and NIC, simultaneously, using differential pulse voltammetry (DPV). The system with the 2HEAA electrolyte was characterized by cyclic voltammetry and electrochemical impedance spectroscopy, and the DPV parameters were optimized for the best conditions. The method was validated from a calibration curve obtained which showed limit of detection (LOD) of 0.82 and 6.26 μmol L 1 and limit of quantification (LOQ) of 2.73 and 20.8 μmol L-1 for CAF and NIC, respectively. In the precision analyses, values lower than 10% of relative standard deviation were obtained. In the presence of concomitant inorganic and organic species, the system proved to be selective in the determination of analytes. The method was used to determine the analytes in fortified samples (river water, synthetic urine and commercial milk), obtaining recoveries between 87.25 and 111.40%. The 2HEAA demonstrated high efficiency as an alternative electrolyte with good signal-to-noise ratio, increased analytical sensitivity of the method, in addition to presenting low cost and fast electrolyte preparation. (CAF NIC (NIC world work 2hydroxyethylammonium hydroxyethylammonium 2 HEAA (2HEAA simultaneously DPV. . (DPV) spectroscopy conditions LOD (LOD 082 0 82 0.8 626 6 26 6.2 LOQ (LOQ 273 73 2.7 208 20 8 20. L1 L- respectively analyses 10 species river water milk, milk , milk) 8725 87 25 87.2 11140 111 40 111.40% signaltonoise signal noise ratio preparation (DPV 08 0. 62 6. 27 7 2. 872 87. 1114 11 4 111.40 111.4 111.

Palicourea tomentosa (Aubl.) Borhidi (Rubiaceae, Palicoureeae), earlier classified as Psychotria poeppigiana Müll. Arg., is used in folk medicine for a variety of diseases. Biological studies on the plant describes their vasorelaxant, antiplasmodial, antitumoural and anticholinesterase activities. To expand the knowledge on the chemical and biological potential of this species, in this work, phytochemical and dereplication studies, as well as antimicrobial and anticholinesterase evaluation of Palicourea tomentosa were carried out. Phytochemical investigation deals with the isolation of lutein (1), a mixture of dehydrovomifoliol (2) and megastigma-4,7-dien-3-one (3), loliolide (4), 5,13-epoxy-9-hydroxy-megastigma-7-en,3-one (5), vomifoliol (6), asperuloside (7), 3-O-p-coumaroylquinic acid (8), and a mixture of the pyrrolizidinoindoline alkaloids hodgkinsine (9), chimonanthine (10) and psychotriasine (11). The ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC HRMS/MS) based on molecular networking dereplication of dichloromethane fraction led to putative identification of other two megastigmanes, one terpene lactone and three carotenoids, besides seven triterpenes and four indole alkaloids. The dichloromethane, ethyl acetate and hydromethanol fractions of P. tomentosa were able to inhibit Candida albicans with minimum inhibitory concentrations (MICs) of 125, 250 and 125 µg mL-1, respectively. The methanol crude extract, dichloromethane and alkaloid fractions inhibited selectively the butyrilcholinesterase (BuChE) at percentages of 63.09, 60.39 and 56.22%, respectively. Aubl. Aubl (Aubl. Rubiaceae, Rubiaceae (Rubiaceae Palicoureeae, Palicoureeae , Palicoureeae) Müll Arg Arg. diseases vasorelaxant antiplasmodial activities species work out 1, 1 (1) 2 (2 megastigma4,7dien3one megastigma47dien3one megastigmadienone megastigma 4,7 dien 3 4 7 3, (3) 4, (4) 5,13epoxy9hydroxymegastigma7en,3one 513epoxy9hydroxymegastigma7en3one epoxyhydroxymegastigmaenone 5,13 epoxy 9 hydroxy en,3 5 13 en 5, (5) 6, 6 (6) 7, (7) 3Opcoumaroylquinic Opcoumaroylquinic O p coumaroylquinic 8, 8 (8) 9, (9) 10 (10 11. 11 . (11) ultrahigh ultra high highresolution resolution UHPLC HRMS/MS HRMSMS HRMS MS megastigmanes carotenoids P MICs (MICs 25 12 mL1, mL1 mL mL-1 respectively extract BuChE (BuChE 6309 63 09 63.09 6039 60 39 60.3 5622 56 22 56.22% (Aubl (1 ( megastigma4 7dien3one 47 (3 (4 13epoxy9hydroxymegastigma7en 3one hydroxymegastigma 513 5,1 en3 en, (5 (6 (7 (8 (9 (11 mL- 630 0 63.0 603 60. 562 56.22 dienone epoxyhydroxymegastigmaen 51 63. 56.2 56.

ABSTRACT Introduction: The validation of analytical methods ensures the reproducibility of data, when it is desired to perform the quantification of a product, using methodologies different from those established in official documents. Objective: Validate an analytical method by UV Vis spectrophotometry for the quantification of total alkaloids. Methods: A galenic preparation containing 0.1% of belladonna extract was used to determine the validation parameters using a UV-visible spectrophotometric method at 435 nm, based on the precipitation of alkaloids by interaction with the Dragendorff's reagent. Specificity used a concentration of 100%, while linearity required samples of 80%, 90%, 100%, 110% and 120%; and, in the case of the range, at 80% and 120%. Precision evaluated repeatability at 80%, 100% and 120%, and intermediate precision required a 100% sample considering inter-analyst, inter-team and inter-day conditions. Finally, in accuracy, concentrations of 80%, 100% and 120%; and, for robustness, a 100% sample was analyzed to determine pH variation and centrifugation speed. Results: The selectivity obtained acceptable values in both the matrix and the elaborated product, the linearity presented correlation and determination coefficients close to 1, and the concentration range was between 40 - 60 mg/L. Accuracy, precision and robustness had a variability of less than 2%. Conclusions: The UV Vis spectrophotometric method is selective, linear, exact, precise and robust; it is reliable in the determination of precipitable alkaloids.

RESUMEN Introducción: La validación de métodos analíticos asegura la reproducibilidad de datos cuando se desea realizar la cuantificación de un producto, mediante metodologías diferentes a las establecidas en documentos oficiales. Objetivo: Validar un método analítico por espectrofotometría ultravioleta-visible para la cuantificación de alcaloides totales. Métodos: Se utilizó un preparado galénico que contiene 0,1 % de extracto de belladona para determinar los parámetros de validación mediante un método espectrofotométrico ultravioleta-visible a 435 nm, a partir de la precipitación de alcaloides por la interacción con el reactivo de Dragendorff. La especificidad utilizó una concentración de 100 %, mientras, linealidad requirió muestras de 80 %, 90 %, 100 %, 110 % y 120 %; y, en el caso del rango, al 80 % y 120 %. La precisión evaluó la repetibilidad al 80 %, 100 % y 120 %, y, la precisión intermedia requirió una muestra al 100 % considerando condiciones interanalistas, interequipos e interdías. Finalmente, en exactitud, concentraciones de 80 %, 100 % y 120 %; y, en robustez se analizó una muestra al 100 % para determinar variación de pH y velocidad de centrifugación. Resultados: La selectividad obtuvo valores aceptables tanto en la matriz como el producto elaborado, la linealidad presentó coeficientes de correlación y determinación próximos a 1, y el rango de concentración se encontró entre 40 - 60 mg/L. Exactitud, precisión y robustez tuvieron una variabilidad menor al 2 %. Conclusiones: El método espectrofotométrico ultravioleta-visible es selectivo, lineal, exacto, preciso y robusto; es confiable en la determinación de alcaloides precipitables.

Abstract In the pre-Columbian societies of the Americas, a wide range of food practices was observed. However, several countries shared certain staple foods, such as the potato, which has held a significant place in the diet since ancient times. It is important to note that potatoes contain glycoalkaloids, a class of alkaloids with potential toxicity risks when consumed in high concentrations by both humans and animals. This study aims to offer guidance on the presence of glycoalkaloids in potatoes and proposes further research into these compounds in archaeological remains that were utilized as food across all American countries. This recommendation stems from the dearth of studies on this subject, particularly in cases where archaeological discoveries include potato starch granules. In this study, various databases were examined to discover historical insights into the potato and to elucidate the primary aspects of glycoalkaloid chemistry associated with this tuber. The findings underscore the crucial role played by the potato in pre-Columbian cultures of the Americas, particularly in the regions situated along the Andes mountain range. Furthermore, the analysis of its nutritional composition unveiled the prevalence of two key glycoalkaloids in the tuber: α-solanine and α-chaconine. In this research, a comprehensive review of the chemical properties, botanical functions, human metabolism, potential health effects, toxicity thresholds, and available analytical techniques for the detection and quantification of toxic compounds was conducted. The significance of identifying these molecules in archaeological contexts was highlighted, as their presence may prompt investigations into prevalent diseases among historical populations.

Resumen En todo el continente americano, las sociedades precolombinas mostraron prácticas alimentarias diversas; no obstante, diferentes países compartían alimentos comunes. Un ejemplo es la papa, un tubérculo que ha sido un alimento básico en la dieta desde la antigüedad. Las papas contienen glicoalcaloides, una clase de alcaloides que, cuando se ingieren en concentraciones elevadas, pueden plantear riesgos de toxicidad tanto para los seres humanos como para los animales. El objetivo de este estudio es ofrecer una guía sobre glicoalcaloides presentes en papas, y recomendar que se realice investigación de estos compuestos en materiales arqueológicos que fueron destinados para alimentos en todos los países de América. Esta sugerencia surge de la ausencia de estudios de esta naturaleza, particularmente cuando los hallazgos arqueológicos incluyen gránulos de almidón de papa. Se revisaron varias bases de datos para encontrar información histórica sobre la papa e indicar los principales aspectos de la química de los glicoalcaloides relacionados con el tubérculo. Los principales hallazgos indican la importancia que representó la papa en las culturas precolombinas de América, especialmente en las regiones situadas a lo largo de la cordillera de los Andes. La investigación de la composición nutricional reveló que en el tubérculo se pueden encontrar dos glicoalcaloides predominantes: α-solanina y α-chaconina. Se realizó un análisis bibliográfico de estos compuestos tóxicos para comprender su importancia, propiedades químicas, funciones botánicas, metabolismo en el ser humano junto con los posibles problemas de salud, umbrales de toxicidad y las diversas técnicas analíticas disponibles para su detección y cuantificación. La identificación de estas moléculas adquiere importancia en contextos arqueológicos, ya que su presencia puede dar lugar a investigaciones sobre posibles enfermedades prevalentes en la población de la época.

Abstract Mexico is the largest exporter of chili peppers and the second largest producer worldwide, due to which large quantities of biomass are produced, which are not always treated in a sustainable way, which can have a negative impact on the environment. One of the utilization trends is their use to obtain nutraceuticals. This research aimed to determine the phytochemicals present in poblano, jalapeno, and bell pepper biomasses produced in Culiacán, Sinaloa, Mexico, as well as to evaluate their antioxidant activity. The study was conducted in 2022. Phytochemical screening was performed and total free and bound phenolic compounds, flavonoids, antioxidant activity, capsaicinoids, and volatile compounds were quantified. Chili pepper biomasses are an important source of free phenols (1 010.14 ±41.81 mg GAE 100 g-1), bound phenols (158.66 ±8.87 mg GAE 100 g-1), flavonoids (158 ±8.87 mg QE 100 g-1), dihydrocapsaicin (1.762 μg kg-1), phytosterols, terpenes, tannins, saponins, and alkaloids (atropine), in addition to presenting antioxidant activity (35 744.04 ±618.6 μmol TE 100 g-1). It was concluded that biomasses contain biofunctional nutraceuticals, so their valorization for this purpose can promote the generation of circular economies in Mexico.

Resumen México es el principal exportador de chile y segundo productor a nivel a mundial, debido a esto se producen grandes cantidades de biomasas, las cuales no siempre son tratadas de forma sustentable, pudiendo ejercer un impacto negativo al medio ambiente. Una de las tendencias de aprovechamiento, es su uso para la obtención de nutracéuticos. El objetivo de la investigación fue determinar los fitoquímicos presentes en las biomasas de chile poblano, jalapeño y pimiento morrón producidas en Culiacán, Sinaloa, México, así como evaluar su actividad antioxidante. El estudio se realizó durante 2022. Se realizó un tamizaje fitoquímico y se cuantificaron los compuestos fenólicos totales libres y ligados, flavonoides, actividad antioxidante, capsaicinoides y compuestos volátiles. Las biomasas de chile son una fuente importante de fenoles libres (1 010.14 ±41.81 mg EAG 100 g-1), ligados (158.66 ±8.87 mg EAG 100 g-1) flavonoides (158 ±8.87 mg EQ 100 g-1), dihidrocapsaicina (1.762 µg kg-1), fitoesteroles, terpenos, taninos, saponinas, y alcaloides (atropina) además de presentar actividad antioxidante (35 744.04 ±618.6 µmol ET 100 g-1). Se concluyó que las biomasas contienen nutracéuticos biofuncionales, por lo que su valorización para este fin puede promover la generación de economías circulares en México.

Abstract The objective of the study was to carry out phytochemical prospection through colorimetric tests to determine the groups of secondary metabolites and also to determine the total content of phenolic compounds (TPC) present in plant extracts methanol (ME), ethyl acetate (EAE), hexane (HE) and dichloromethane (DE) from the leaves of Myrsine umbellata, as well as to investigate the antimicrobial activity against twelve standard ATCC strains by the broth microdilution technique; the antioxidant potential by the DPPH method and the ABTS method and the antibiofilm potential on the biofilm biomass of standard bacteria by the crystal violet technique and tetrazolium salt reduction (MTT) assay. Phytochemical prospection detected the presence of saponins, steroids, alkaloids, anthocyanins, anthocyanidins, flavonoids, and tannins. The results of the quantitative phytochemical estimation revealed a higher content of total phenolics in DE (280.24 ± 0.037 µM GAE g ext. -1) followed by ME (159.01 ± 0.031 µM GAE g ext. -1). The ME showed the best biological activities when compared to the other extracts tested. We observed antimicrobial activity against Gram-positive Staphylococcus epidermidis strain (MIC 3.12 and MBC 6.25), antioxidant percentage of 92.58% against the DPPH radical and 420.31 µM Trolox g ext. -1 against the ABTS radical, finally showed antibiofilm action against Gram-positive strain Staphylococcus aureus, with eradication of the biomass in 92.58%. The results suggest that EM from M. umbellata represents an alternative source of plant bioactives for the development of natura products. TPC (TPC ME, , (ME) EAE, EAE (EAE) HE (HE (DE MTT (MTT assay saponins steroids alkaloids anthocyanins anthocyanidins flavonoids tannins 280.24 28024 280 24 (280.2 0037 0 037 0.03 ext 1 159.01 15901 159 01 (159.0 0031 031 1. . tested Grampositive Gram positive MIC 312 3 12 3.1 6.25, 625 6.25 6 25 6.25) 9258 92 58 92.58 42031 420 31 420.3 - aureus M products (ME (EAE 280.2 2802 28 2 (280. 003 03 0.0 159.0 1590 15 (159. 3. 62 6.2 925 9 5 92.5 4203 42 420. 280. (280 00 0. 159. (159 6. 92. 4 (28 (15 (2 (1 (

Resumo O objetivo do estudo foi realizar a prospecção fitoquímica através de testes colorimétricos para determinar os grupos de metabólitos secundários e também determinar o teor total dos compostos fenólicos (TPC) presente nos extratos vegetais metanol (EM), acetato de etila (EAE), hexano (EH) e diclorometano (ED) das folhas de Myrsine umbellata, bem como investigar a atividade antimicrobiana contra doze cepas padrão ATCC pela técnica de microdiluição em caldo; o potencial antioxidante pelo método DPPH e pelo método ABTS e o potencial antibiofilme sobre a biomassa padrão de biofilmes bacterianos pela técnica do cristal violeta e ensaio de redução do sal de tetrazólio (MTT). A prospecção fitoquímica detectou a presença de saponinas, esteróides, alcaloides, antocianinas, antocianidinas, flavonoides e taninos. Os resultados da estimativa fitoquímica quantitativa revelaram maior teor de fenólicos totais em ED (175,15 ± 0,037 µM GAE g ext. -1) seguido de EM (159,02 ± 0,031 µM GAE g ext. -1). O EM apresentou as melhores atividades biológicas quando comparado aos demais extratos testados, observamos atividade antimicrobiana contra cepa Gram-positiva S. epidermidis (MIC 3.12 e MBC 6.25), percentual antioxidante de 92,58% frente ao radical DPPH e 420,44 mg Trolox g ext. -1 frente ao radical ABTS, por fim apresentou ação antibiofilme contra cepa Gram-positiva S. aureus, com erradicação da biomassa em 92,58%. Os resultados sugerem que o EM de M. umbellata representa uma fonte alternativa de bioativos vegetais para o desenvolvimento de produtos em natura. TPC (TPC EM, , (EM) EAE, EAE (EAE) EH (EH (ED caldo MTT. MTT . (MTT) saponinas esteróides alcaloides antocianinas antocianidinas taninos 175,15 17515 175 15 (175,1 0037 0 037 0,03 ext 1 159,02 15902 159 02 (159,0 0031 031 1. testados Grampositiva Gram positiva S MIC 312 3 12 3.1 6.25, 625 6.25 6 25 6.25) 9258 92 58 92,58 42044 420 44 420,4 - aureus M natura (EM (EAE (MTT 175,1 1751 17 (175, 003 03 0,0 159,0 1590 (159, 31 3. 62 6.2 2 925 9 5 92,5 4204 42 4 420, 175, (175 00 0, 159, (159 6. 92, (17 (15 (1 (

Abstract The Astragalus grahamianus (AG) Royle ex. Benth is traditionally used for the treatment of various human disorders. The current research work is aimed to explore the neuroprotective anti-Parkinson effects of various fractions of Astragalus grahamianus (A. grahamianus). Fine powder of Astragalus grahamianus was extracted with 70% methanol and then fractionated with various solvents on the basis of polarity. Standard protocols were used to investigate the bioactive constituents present in the various plant fractions. In-vitro antioxidant potential of various fractions was checked using diverse free radicals. In-vivo rats model was used to determined the neuroprotective effects of methanol fraction of A. grahamianus. The results revealed that various fractions of A. grahamianus contain flavonoids, cardiac glycosides, steroids, gums, terpenes, proteins, and carbohydrates except chloroform fraction lake the presence of steroids, cardiac glycosides, gums and saponins, aqueous fraction of steroids, terpenoids, gums and saponins, n-Hexane fraction steroids, carbohydrates, alkaloids, gums and flavonoids. The highest amount of total phenolic contents was found in AGME (32.67 ± 2.3 mg GAE / g). The AGME also showed enhanced free radicals cations potential against DPPH, ABTS and H2O2, respectively. The correlation between AOA (antioxidant activity) and TPC (total phenolic contents) revealed to be substantial. Relative R2 values for ABTS, H2O2, and DPPH activity are 0.9974, 0.9845, and 0.9678, respectively. The in-vivo neuroprotective activities showed significant results. Our findings highlight significant antioxidant, and neuroprotective possessions of AGME attributed to powerful bioactive compounds. AG (AG ex disorders antiParkinson anti Parkinson A (A . grahamianus) 70 polarity Invitro In vitro Invivo vivo flavonoids glycosides steroids terpenes proteins saponins terpenoids nHexane n Hexane alkaloids 32.67 3267 32 67 (32.6 23 2 3 2. g. g g) H2O2 HO H O respectively substantial R 09974 0 9974 0.9974 09845 9845 0.9845 09678 9678 0.9678 invivo compounds 7 32.6 326 6 (32. H2O 0997 997 0.997 0984 984 0.984 0967 967 0.967 32. (32 099 99 0.99 098 98 0.98 096 96 0.96 (3 09 9 0.9 ( 0.

Resumo O Astragalus grahamianus (AG) Royle ex. Benth pertence à família Fabaceae e o gênero Astragalus é tradicionalmente utilizado para o tratamento de diversas doenças humanas. O presente trabalho de pesquisa tem como objetivo explorar os aspectos benéficos das plantas que estão sendo investigados tanto in vitro, ou seja, antioxidantes, quanto in vivo (seu impacto no comprometimento da memória induzido pela neuroinflamação em ratos). Para tanto, extrato metanólico de A. grahamianus (AGME) e frações com diversos solventes foram sintetizados com base na polaridade. Os resultados revelaram que várias frações de A. grahamianus contêm flavonoides, glicosídeos cardíacos, esteroides, gomas, terpenos, proteínas e carboidratos, exceto a fração de clorofórmio, e a presença de esteroides, glicosídeos cardíacos, gomas e saponinas, fração aquosa de esteroides, terpenoides, gomas e saponinas, esteroides da fração n-hexano, carboidratos, alcaloides, gomas e flavonoides. A maior quantidade de conteúdo fenólico total foi encontrada no AGME (32,67 ± 2,3 mg GAE/g). O AGME também mostrou maior potencial de cátions de radicais livres contra DPPH, ABTS e H2O2. A correlação entre AOA (atividade antioxidante) e TPC (conteúdo fenólico total) revelou-se substancial. Os valores relativos de R2 para atividade ABTS, H2O2 e DPPH são 0,9974, 0,9845 e 0,9678, respectivamente. As atividades neuroprotetoras in vivo mostraram resultados significativos. Nossas descobertas destacam propriedades antioxidantes e neuroprotetoras significativas do AGME atribuídas a poderosos compostos bioativos. AG (AG ex humanas vitro seja seu ratos. ratos . ratos) (AGME polaridade flavonoides cardíacos terpenos carboidratos clorofórmio saponinas terpenoides nhexano, nhexano n hexano, hexano n-hexano alcaloides 32,67 3267 32 67 (32,6 23 2 3 2, GAE/g. GAEg GAE/g GAE g GAE/g) HO H antioxidante revelouse revelou se substancial R H2O 09974 0 9974 0,9974 09845 9845 0,984 09678 9678 0,9678 respectivamente significativos bioativos 32,6 326 6 (32, 0997 997 0,997 0984 984 0,98 0967 967 0,967 32, (32 099 99 0,99 098 98 0,9 096 96 0,96 (3 09 9 0, (

Abstract Plants that produce allelopathic compounds against weeds have emerged as a potential solution for the development of ecologically correct bioherbicides. Talinum triangulare is noteworthy in this regard, as its phytochemical composition encompasses flavonoids, alkaloids and other metabolites that can be used to develop inhibitory weed growth solutions. Lactuca sativa (lettuce) has been widely applied as a bioindicator species for bioherbicides and several chemicals, animal waste, water and soil quality, and atmospheric contamination, among others. In this context, this study aimed to assess the potential allelopathic effect of aqueous T. triangulare extracts on the development of L. sativa seedlings. A completely randomized design employing a 2x4 factorial scheme (shoot and root extracts) x the concentration of each extract (0, 2.5, 5, 7.5%) was applied, comprising four replications. Lactuca sativa seeds were sown on germitest papers soaked with the extracts in a germination chamber at 20°C. Physiological seed evaluations comprising the germination test, where normal and abnormal seedlings are counted on the seventh day after sowing, first normal seedling counts on the fourth day after sowing, and seedling and root length measurements. At the end of the germination test, L. sativa seedlings were separated for morphoanatomical characterizations and chlorophyll a fluorescence analyses. The T. triangulare extracts significantly influenced L. sativa root growth, with shoot extract exposure leading to more abnormal plants and lower root lengths at increasing concentrations and compared to the root extract. Root extract exposure led to evident cellular changes and lower non-photochemical quenching and unregulated dissipation quantum yields at a 5% exposure dose compared to shoot extract exposure. These findings suggest that both aqueous T. triangulare root and shoot extracts from 5% exposure doses exhibit high potential as bioherbicides, acting directly on plant structure, anatomy, quality, size and physiology. regard flavonoids solutions lettuce (lettuce chemicals waste quality contamination others context T L 2x 0, 0 (0 25 2 5 2.5 7.5% 75 7 replications 20C C 20 20°C test sowing measurements analyses nonphotochemical non photochemical structure anatomy physiology ( 2. 7.5 7.

Resumo Espécies vegetais que possuem substância com efeitos alelopáticos contra plantas daninhas são potenciais soluções para o desenvolvimento de bioherbicidas ecologicamente corretos. Dentre as espécies com potencial de alelopatia, Talinum triangulare apresenta em sua composição fitoquímica flavonoides, alcaloides e outros metabólitos que podem ser utilizados para o desenvolvimento de soluções inibitórias do crescimento de plantas daninhas. Já a planta Lactuca sativa é bastante utilizada há vários anos como espécie bioindicadora, tanto para bioherbicidas, como para químicos em geral, resíduos animais, qualidade de água e solo, contaminação atmosférica e outros. Nesse cenário, objetivou-se avaliar o potencial efeito alelopático dos extratos aquosos de T. triangulare no desenvolvimento de plântulas de Lactuca. sativa. O delineamento utilizado foi inteiramente ao acaso, com esquema fatorial 2x4 (extratos de parte aérea e raiz) x concentrações de cada extrato (0; 2,5; 5; 7,5%), com quatro repetições. Para imposição dos tratamentos, as sementes de Lactuca sativa foram semeadas sobre os papéis embebidos com os extratos e o material foi acondicionado em câmara de germinação a 20°C. Foram realizadas as avaliações fisiológicas das sementes, sendo elas: teste de geminação (plântulas normais e anormais ao sétimo dia após a semeadura), 1° contagem de plântulas normais ao quarto dia após a semeadura, o comprimento de plântulas e comprimento de raiz. Ao final do teste de germinação foram coletadas plântulas de L. sativa para caracterização morfoanatômica e análise de fluorescência da clorofila a. Os extratos de T. triangulare influenciaram no crescimento de raízes de L. sativa, e os extratos aquosos de T. triangulare da parte aérea influenciaram em maior valor de plantas anormais, juntamente com menor comprimento de raiz tanto em relação ao aumento da concentração quanto em comparação com o extrato da raiz. Além disso, o extrato de raiz influenciou em alterações celulares evidentes e menor quenching não fotoquímico e rendimentos quânticos de dissipação não regulada para a dosagem de 5% em comparação com a parte aérea. Dessa forma, sugere-se que o extrato aquoso tanto da raiz quando da parte aérea de T. triangulare a partir da dosagem de 5% tem grande potencial para o uso como bioherbicidas atuando diretamente na estrutura, anatomia, qualidade, tamanho, fisiologia das plantas. corretos alelopatia flavonoides bioindicadora geral animais solo cenário objetivouse objetivou se T acaso 2x 0 (0 2,5 25 2 5 7,5%, 75 7,5% , 7 7,5%) repetições tratamentos 20C C 20 20°C elas semeadura semeadura) 1 L disso forma sugerese sugere estrutura anatomia tamanho ( 2, 7,5 7,

Resumo Crotalaria (Linnaeus, 1753) (Fabaceae) ocorre abundantemente em regiões tropicais e subtropicais e tem cerca de 600 espécies conhecidas. Estas plantas são amplamente utilizadas na agricultura, principalmente como cobertura e adubos verdes, além da sua utilização no manejo de fitonematoides. Uma característica marcante destas espécies é a produção de alcalóides pirrolizidinicos (APs), aleloquímicos secundários envolvidos na defesa das plantas contra os herbívoros. Nas espécies de Crotalaria, a monocrotalina é a AP predominante, que tem muitas atividades biológicas relatadas, incluindo citotoxicidade, tumorigenicidade, hepatotoxicidade e neurotoxicidade, além de uma vasta gama de interações ecológicas. Assim, estudos têm procurado elucidar os efeitos desse composto para promover um incremento na flora e fauna (principalmente insetos e nematoides) associados aos agroecossistemas, favorecendo o controle biológico natural. Esta revisão compila informações sobre a monocrotalina, mostrando tais efeitos nesses ambientes, tanto acima como abaixo do solo e a sua potencial utilização em programas de manejo de pragas.

Abstract Crotalaria (Fabaceae) occurs abundantly in tropical and subtropical regions and has about 600 known species. These plants are widely used in agriculture, mainly as cover plants and green manures, in addition to their use in the management of phytonematodes. A striking feature of these species is the production of pyrrolizidine alkaloids (PAs), secondary allelochemicals involved in plant defense against herbivores. In Crotalaria species, monocrotaline is the predominant PA, which has many biological activities reported, including cytotoxicity, tumorigenicity, hepatotoxicity and neurotoxicity, with a wide range of ecological interactions. Thus, studies have sought to elucidate the effects of this compound to promote an increase in flora and fauna (mainly insects and nematodes) associated with agroecosystems, favoring the natural biological control. This review summarizes information about the monocrotaline, showing such effects in these environments, both above and below ground, and their potential use in pest management programs.

Resumo Este estudo teve como objetivo investigar o impacto do extrato da folha de Vernonia amygdalina na regulação do FLT3. V. amygdalina foi extraída com etanol 96% (VAE-96) e sua citotoxicidade contra linhagens celulares FLT3 (MOLM-13 e MV-4-11) foi avaliada. Os resultados indicaram que o VAE-96 induziu apoptose nestas células e inibiu a fosforilação de AKT, MAPK e FLT3. Além disso, o VAE-96 diminuiu substancialmente a atividade do promotor FLT3 e a expressão do mRNA do FLT3. Descobriu-se que o extrato contém alcaloides, saponinas, compostos de açúcar reduzido e polifenóis, incluindo taninos e flavonoides, conforme análise de fitoconstituintes. O potencial das frações alcaloides nas células MOLM-13 foi indicado pelo intenso efeito citotóxico das frações alcaloides, que resultou em mais de 50% de mortalidade celular a 30 µg/ml. Nossos resultados sugerem que o VAE-96 pode ser um agente benéfico para a prevenção e tratamento da LMA com mutação FLT3-ITD. FLT V 96 VAE96 VAE (VAE-96 MOLM13 MOLM 13 (MOLM-1 MV411 MV 4 11 MV-4-11 avaliada VAE-9 AKT disso Descobriuse Descobriu se saponinas polifenóis flavonoides fitoconstituintes MOLM-1 50 3 µgml µg ml µg/ml FLT3ITD. FLT3ITD FLTITD ITD. ITD FLT3-ITD 9 VAE9 (VAE-9 MOLM1 1 (MOLM- MV41 MV-4-1 VAE- MOLM- 5 (VAE- (MOLM MV4 MV-4- (VAE MV-4 MV-

Abstract This study aimed to investigate the impact of Vernonia amygdalina leaf extract on FLT3 regulation. V. amygdalina was extracted with 96% ethanol (VAE-96), and its cytotoxicity against FLT3- cell lines (MOLM-13 and MV-4-11) was evaluated. The results indicated that VAE-96 induced apoptosis in these cells and inhibited the phosphorylation of AKT, MAPK, and FLT3. Additionally, VAE-96 substantially diminished the activity of the FLT3 promoter and the expression of FLT3 mRNA. The extract was found to contain alkaloids, saponin, reduced sugar compounds, and polyphenols, including tannins and flavonoids, as per the phytoconstituents analysis. The potential of alkaloid fractions on MOLM-13 cells was indicated by the robust cytotoxic effect of the alkaloid fractions, which resulted in over 50% cell mortality at 30 µg/ml. Our results suggest that VAE-96 may be a beneficial agent for the prevention and treatment of AML with FLT3-ITD mutation. FLT regulation V 96 VAE96, VAE96 VAE , (VAE-96) MOLM13 MOLM 13 (MOLM-1 MV411 MV 4 11 MV-4-11 evaluated VAE-9 AKT MAPK Additionally mRNA alkaloids saponin compounds polyphenols flavonoids analysis MOLM-1 50 3 µgml µg ml µg/ml FLT3ITD FLTITD ITD mutation 9 VAE9 (VAE-96 MOLM1 1 (MOLM- MV41 MV-4-1 VAE- MOLM- 5 (VAE-9 (MOLM MV4 MV-4- (VAE- MV-4 (VAE MV-

In recent years, there has been great interest in understanding the chemistry of natural products from different organisms and their role in ecological processes. Some species of frogs sequester and metabolize dietary alkaloids obtained primarily from mites and ants as chemical defense. Most of these studies have employed gas chromatography techniques coupled with mass spectrometry, which restricts the possibility of observing more polar metabolites. In the case of pumiliotoxin (+)-251D and allopumiliotoxin (+)-267A, the fragmentation mechanisms in electrospray ionization systems with collision-induced fragmentation are undescribed. The present study aims to elucidate the fragmentation pathways of these two toxins. For this purpose, we used direct infusion of toxins in a time-of-flight hyphenated quadrupole electrospray ionization tandem mass spectrometry (ESI-MS/MS) system. Different collision energies were applied, and the data rationalized from the concepts of reaction mechanisms. The joint analysis allowed to present a robust map of fragmentation opening perspectives for their application in studies of the occurrence of new polar analogues. years processes defense metabolites +251D 251D D + +267A, 267A A 267A, (+)-267A collisioninduced induced undescribed purpose timeofflight time flight ESIMS/MS ESIMSMS ESI MS/MS MS (ESI-MS/MS system applied analogues +267A ESIMS MSMS

ABSTRACT Fusarium species are the cause of diseases in various crops throughout the world and cause significant economic losses. Chemical fungicides are the main strategy for control, but their intensive and long-term use generates resistance, toxic residues, and environmental contamination. The biological control of bioactive substances has wide applications. In this study, the fungicidal activity of the extract obtained from Annona glabra L. seeds was evaluated as a control alternative for Fusarium solani. In addition, chemical characterization was carried out to identify the groups of metabolites present in the extract. The fungicidal activity against F. solani was evaluated using the microdilution method, and the minimum inhibitory concentration (MIC) was established, as well as the mean inhibitory concentration (IC50). The IC50 of the extract was 972.24 mg L-1, and the MIC was 12.02 mg L-1. Using chemical characterization by ultrahigh-efficiency liquid chromatography coupled with mass spectrometry, the presence of THF acetogeniones, isoquinolinic alkaloids, and kaurene-type diterpenes, which were the main compounds responsible for the activity evaluated, was confirmed. The results obtained provide evidence that A. glabra seed extracts can be a potential source of metabolites with fungicidal activity. losses longterm long term resistance residues contamination applications study L addition F method (MIC established IC50. IC . (IC50) IC5 97224 972 24 972.2 L1, L1 1, 1 L-1 1202 12 02 12.0 L1. 1. ultrahighefficiency ultrahigh efficiency spectrometry acetogeniones alkaloids kaurenetype kaurene type diterpenes confirmed A (IC50 9722 97 2 972. L- 120 0 12. (IC5 9 (IC

RESUMO O gênero Fusarium é causador de doenças em diversas culturas agrícolas em todo o mundo com perdas econômicas significativas. Os fungicidas químicos são a principal estratégia de controle, mas o seu uso intensivo e prolongado gera resistência, resíduos tóxicos e contaminação ambiental. O controle biológico a partir de substâncias bioativas tem ampla aplicação. Neste estudo, a atividade fungicida do extrato obtido de Annona glabra L. como alternativa ao controle de Fusarium solani. Além disso, foi realizada uma caracterização química com o intuito de identificar os grupos de metabólitos presentes no extrato. A atividade fungicida contra F. solani foi avaliada pelo método de microdiluição e foi estabelecida a concentração inibitória mínima (CIM) e a concentração inibitória média (IC50). Os resultados da atividade fungicida mostraram que o IC50 do extrato foi de 972.24 mg L-1 e o MIC foi de 12.02 mg L-1. Através da caracterização química por cromatografia líquida de ultraalta eficiência acoplada à espectrometria de massas (UHPLC-MS/ MS), foi confirmada a presença de acetogênios THF, alcaloides isoquinolínicos e diterpenos do tipo caureno, que são os principais responsáveis pela atividade avaliada. Os resultados obtidos fornecem evidências de que os extratos de sementes de A. glabra podem ser uma fonte potencial de metabólitos com atividade fungicida contra F. solani. significativas resistência ambiental aplicação estudo L disso F CIM (CIM IC50. IC . (IC50) IC5 97224 972 24 972.2 L1 1 L- 1202 12 02 12.0 L1. 1. UHPLCMS/ UHPLCMS UHPLC MS/ MS (UHPLC-MS MS, , MS) THF caureno (IC50 9722 97 2 972. 120 0 12. (IC5 9 (IC

Phytochemical study of Psychotria schlechtendaliana (Rubiaceae) aerial parts resulted in the isolation of alkaloids 4 N oxide harmane (1) and strictosidinic acid (2), and the terpenoids sitosterol, estigmasterol, α-amyrin, β-amyrin and betulinic acid. The crude extract (CE), its fractions (hexane FH, chloroform FC, ethyl acetate FEA, hydromethanolic FHM, alkaloidal chloroform FCOH, alkaloidal aqueous FAq) and majority alkaloid (1) were investigated for their antiproliferative potential against nine human tumor cells lines and one non-tumoral human cell line (HaCat). CE, FH and FEA fractions exhibited strong growth inhibition for ovary cells (OVCAR-3, GI50 = 5.89; 1.36 and 6.59 μg mL-1, respectively) and FC, FH and FAq fractions showed potent activity on the growth of leukemia cell lines (K562, GI50 = 1.92; 7.23 and 8.81 μg mL-1, respectively). Compound 1 exhibited selective antiproliferative activity to breast cancer (MCF-7, GI50 = 32.7 μg mL-1) and was non-toxic to HaCat cells. To evaluate the anti-inflammatory effect, models of ear edema induced by croton oil and the enzyme myeloperoxidase (MPO) were used. FH and FC fractions exhibited anti-inflammatory effect and reduce ear edema compared to the control group. These fractions showed results superior to those exhibited by indomethacin (75.1%), FH (97.5%) and FC (95.5%) fractions. Rubiaceae (Rubiaceae (1 2, 2 , (2) sitosterol estigmasterol αamyrin, αamyrin α amyrin, amyrin α-amyrin βamyrin β CE (CE) hexane FHM FCOH nontumoral non tumoral HaCat. . (HaCat) OVCAR3, OVCAR3 OVCAR 3, 3 (OVCAR-3 GI GI5 5.89 589 5 89 136 36 1.3 659 6 59 6.5 mL1, mL1 mL 1, mL-1 respectively K562, K562 K (K562 1.92 192 92 723 7 23 7.2 881 8 81 8.8 respectively. MCF7, MCF7 MCF 7, (MCF-7 327 32 32. nontoxic toxic antiinflammatory anti inflammatory MPO (MPO used group 75.1%, 751 75.1% 75 (75.1%) 97.5% 975 97 (97.5% 95.5% 955 95 (95.5% ( (2 (CE (HaCat (OVCAR- 5.8 58 13 1. 65 6. mL- K56 (K56 1.9 19 9 72 7. 88 8. (MCF- 75.1 (75.1% 97.5 (97.5 95.5 (95.5 (OVCAR 5. K5 (K5 (MCF 75. (75.1 97. (97. 95. (95. (K (75. (97 (95 (75 (9 (7

Coronavirus disease (COVID-19) pandemic has infected 630 million people and led to 6.59 million deaths worldwide since its outbreak. To control COVID-19 advance, finding new molecules with potential to inhibit viral spread is pivotal. Papain-like protease (PLpro) is one of the most interesting targets of pharmacological inhibition since it is implicated not only in viral replication but also in modulation of host immune response. Natural products are of great interest to the pharmaceutical industry due to their diverse structure and biological activities. The NuBBEDB (Nuclei of Bioassays, Biosynthesis and Ecophysiology of Natural Products Database) is an excellent source of natural products (NPs) from the Brazilian flora. In this study, we performed virtual screening, molecular dynamics, and binding energy analyses of the NuBBEDB library to target severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) papain-like protease (PLpro), the virus’s protease essential for replication. Among the top-ranked molecules, the indole alkaloids raputindoles A, C, and D emerged as potential SARS-CoV-2 inhibitors, showing significant interactions with the pivotal Beta-Loop-2 (BL2) region, including the catalytic Y268 residue. Notably, raputindole D displayed enhanced stabilization of the BL2 region, while raputindole C exhibited superior overall stability. These in silico findings suggest that raputindoles, especially D, might offer therapeutic value against COVID-19, laying the groundwork for further experimental evaluations. COVID19 COVID 19 (COVID-19 63 659 6 59 6.5 outbreak COVID-1 advance Papainlike Papain like PLpro (PLpro response activities Nuclei Bioassays Database NPs (NPs flora study screening dynamics SARSCoV2 SARSCoV SARS CoV (SARS-CoV-2 papainlike papain PLpro, , viruss virus s topranked top ranked A SARS-CoV- inhibitors BetaLoop2 BetaLoop Beta Loop Beta-Loop- BL (BL2 region Y Y26 residue Notably stability COVID19, 19, evaluations COVID1 1 (COVID-1 65 5 6. COVID- (SARS-CoV- SARS-CoV Beta-Loop (BL Y2 (COVID- (SARS-CoV (COVID