Examinando por Autor "Sortino, Maximiliano Andrés"
Mostrando 1 - 17 de 17
Resultados por página
Opciones de ordenación
Ítem Acceso Abierto Catalyst-, solvent- and desiccant-free three-component synthesis of novel C-2,N-3 disubstituted thiazolidin-4-ones(Elsevier, 2016-12-22) Abonia, Rodrigo; Castillo, Juan; Insuasty, Braulio; Quiroga, Jairo; Sortino, Maximiliano Andrés ; Nogueras, Manuel; Cobo, JustoHerein it is provided an efficient, environmentally friendly and one-pot procedure for the synthesis of a library of new and diversely substituted 1,3 thiazolidin-4-ones in short reaction times and good yields through a solvent-, catalyst- and desiccant-free three-component process. Reactions proceeded by treatment of primary benzyl(aryl)amines with aromatic aldehydes (and ketones) and 2-mercaptoacetic acid acting as both reagent and self-catalyst. All reactions were performed in sand bath instead of the commonly used oil bath avoiding the generation of undesired volatile materials proceeding of the thermal decomposition of the oils. IR, Mass and NMR experiments as well as Xray diffraction confirmed structures of the obtained products.Ítem Embargo Desarrollo de fitomedicinas antifúngicas a partir de plantas de la flora argentina(2021) Cordisco, Estefanía; Svetaz, Laura Andrea ; Sortino, Maximiliano AndrésLas infecciones fúngicas han aumentado considerablemente en los últimos años, siendo las ocasionadas por Candida albicans, la principal causa de muerte en individuos inmunocomprometidos. El tratamiento se ve dificultado por el limitado número de drogas antifúngicas en el mercado, cuya eficacia está comprometida por la toxicidad para el hospedero, el estrecho espectro de acción, la emergencia de resistencia y los altos costos. Es por ello que este trabajo se centró en la búsqueda de extractos bioactivos contra C. albicans utilizando nuevas metodologías, como la combinación de extractos naturales con drogas comerciales, con el fin de encontrar actividad antifúngica sinérgica o aditiva; y la irradiación de extractos con luz UV-A, con el fin de excitar moléculas fotoactivas que dañen la levadura mediante estrés oxidativo. Se realizó un screening de 266 extractos obtenidos a partir de 95 especies vegetales argentinas mediante la estrategia clásica (incubación del extracto en solitario con el hongo) y las dos estrategias planteadas anteriormente. Con la estrategia clásica, sólo 28 extractos mostraron actividad en solitario (10,53%). En combinación con antifúngicos comerciales, se obtuvieron 43 extractos activos (16,17%) con al menos uno de los antifúngicos evaluados. Se determinó el tipo de interacción entre 28 extractos activos con itraconazol (ITZ) mediante el método de Tablero de ajedrez, mostrando el 46,43% (13 extractos) interacciones sinérgicas. Se utilizó el programa estadístico Minitab® para evaluar mezclas ternarias manteniendo como componentes comunes, ITZ y un extracto de Zuccagnia punctata, y variando el tercer componente de a uno por vez entre los 12 extractos restantes que habían mostrado sinergismo. Se seleccionaron como mezclas ternarias óptimas aquellas que contenían como tercer componente a los extractos de Ameghinoa patagonica, Scoparia dulcis y Gaillardia megapotamica. Se demostró que las tres mezclas ternarias actuarían por el mecanismo de unión a ergosterol de la membrana fúngica. Mediante la estrategia en combinación con luz, se obtuvieron 31 extractos (11,65%) activos, siendo los extractos hexánico y diclorometánico de raíz de Thymophylla pentachaeta, los más activos. La evaluación de mecanismos fotodinámicos mostró que ambos extractos generan especies reactivas del oxígeno mediante mecanismos tipo I y tipo II. La determinación del espectro de acción evidenció que tanto las mezclas como los extractos fotoactivos poseen actividad contra la mayoría de las especies del género Candida, Cryptococcus neoformans y los dermatofitos ensayados. A través del estudio de la capacidad de inhibición de factores de virulencia fúngicos, se observó que tanto las mezclas como los extractos fotoactivos, disminuyen la adherencia a células epiteliales, la formación de tubo germinativo y pseudomicelio, y la secreción de enzimas hidrolíticas. También se observó que las mezclas inhiben la formación de biofilm y tanto las mezclas como los extractos actúan sobre células de biofilms preformados. Las mezclas formadas por Scoparia dulcis y Ameghinoa patagonica no presentaron actividad citotóxica tanto in vitro como in vivo. Las tres mezclas mostraron actividad antifúngica in vivo en el modelo Caenorhabditis elegans. Estos resultados sientan las bases para el desarrollo de tratamientos alternativos contra C. albicans, con disminuidos efectos adversos respecto de los fármacos antifúngicos ya establecidos.Ítem Acceso Abierto Effects of Chirality on the Antifungal Potency of Methylated Succinimides Obtained by Aspergillus fumigatus Biotransformations. Comparison with Racemic Ones(MDPI Open Access Publishing, 2013-05-15) Sortino, Maximiliano Andrés ; Postigo, Agustina; Zacchino, SusanaEighteen (3R) and (3R,4R)-N-phenyl-, N-phenylalkyl and N-arylsuccinimides were prepared with high enantioselectivity by biotransformation of maleimides with A. fumigatus. This environmentally friendly, clean and economical procedure was performed by the whole-cell fungal bioconversion methodology. Their corresponding eighteen racemic succinimides were prepared instead by synthetic methods. Both, the racemic and the chiral succinimides were tested simultaneously by the microbroth dilution method of CLSI against a panel of human opportunistic pathogenic fungi of clinical importance. Chiral succinimides showed higher antifungal activity than the corresponding racemic ones and the differences in activity were established by statistical methods. The bottlenecks for developing chiral drugs are how to obtain them through a low-cost procedure and with high enantiomeric excess. Results presented here accomplish both these objectives, opening an avenue for the development of asymmetric succinimides as new antifungal drugs for pharmaceutical use.Ítem Acceso Abierto Effects of Larrea nitida nanodispersions on the growth inhibition of phytopathogens(Springer, 2023-09-21) Svetaz, Laura Andrea; Sortino, Maximiliano Andrés; Rocha, Felipe; Nunes Calumby, Rodrigo José; Teixeira Ribeiro Vidigal, Márcia Cristina; Campos Bermúdez, Valeria Alina; Rius, Sebastián Pablo; https://orcid.org/0000-0002-1023-1641; https://orcid.org/0000-0002-4271-1690Larrea nitida Cav. (Zygophyllaceae) is a plant endemic to Argentina and Chile, and its extract has been studied over the last years due to the presence of antimicrobial agents that can be used to control the growth of some pathogens in agriculture. However, the extract is highly hydrophobic, which strongly affects its fungicidal activity in aqueous media. In this sense, the solid dispersion technique was used to produce L. nitida extract nanodispersions with polyethylene glycol (PLE) and with polyethylene glycol and zinc acetate (PZLE). In order to further evaluate the activity of the extract in PLE and PZLE, blank nanodispersions containing only polyethylene glycol (PEG) and zinc acetate (PZ) without the addition of the extract were also produced. The fungicidal activity of the water-soluble nanoparticles was evaluated at different concentrations (0.037–0.110 g.mL−1). In general, the nanoparticles were successfully produced on a nanometric size and presented a significant inhibitory activity on the growth of the pathogens Fusarium oxysporum and Fusarium verticillioides in aqueous media. Compared to PLE, PZLE presented increased fungistatic activity, possibly due to their increased solubility in water. Even though their application in agriculture should be further investigated, the nanodispersions present great potential to be applied as a green biotechnological tool.Ítem Embargo Estudio de Tagetes minuta L. como fuente de moléculas fotosensibilizantes para aplicación en quimioterapia antifúngica fotodinámica(2018) Giacone, Lucía; Sortino, Maximiliano Andrés ; Cordisco, EstefaníaLa Quimioterapia Fotodinámica Antimicrobiana (QTFA), que utiliza compuestos fotosensibilizantes (CF) y luz de una longitud de onda para inducir un daño oxidativo en microorganismos, es un tratamiento alternativo para las infecciones fúngicas superficiales en humanos. Debido a que se ha reportado la presencia de CF en las especies del género Tagetes, se postuló como objetivo de este trabajo, obtener extractos de Tagetes minuta para evaluar su actividad antifúngica frente a hongos patógenos levaduriformes y filamentosos. Se evaluaron 17 extractos, de los cuales 10 resultaron activos, detectándose Concentraciones Inhibitorias Mínimas (CIMs) en luz de entre 250 y 0,49 μg/mL. Los extractos más activos fueron los de raíz, los cuales se seleccionaron para evaluar su acción frente a los factores de virulencia de Candida, observando inhibición de la formación de tubo germinativo y de la adherencia a células epiteliales, como también acción antifúngica contra biofilm. La baja concentración de los extractos que se requiere tanto para matar como para reducir el efecto de los factores de virulencia, tan importantes en la colonización e invasión del huésped, proporcionan evidencia de potenciales antifúngicos naturales que podrían constituir una alternativa interesante para la terapia fotodinámica.Ítem Acceso Abierto First report of canine protothecosis caused by Prototheca wickerhamii in Argentina. Brief literature review(Elsevier, 2025-02-15) Ramadán, Silvana; Bulacio, Lucía; Dalmaso, Hernán; Sepúlveda, Graciela; Sortino, Maximiliano Andrés; Fay, Fabián; Misto, Claudia; Salvador, María Fernanda; Etchecopaz, Alejandro; Cuestas, María Luján; https://orcid.org/0000-0002-9973-1318Protothecosis is an infectious disease caused by microalgae of the genus Prototheca. Prototheca can be found in soil and water and transiently colonize animals. Cutaneous protothecosis can involve not only the skin but also the underlying subcutaneous tissue and lymph nodes. This can lead to clinical signs and a microscopic tissue image that closely resembles a fungal infection. Treatment typically involves antifungal medications. We report the first case of fatal disseminated protothecosis caused by Prototheca wickerhamii in the city of Rosario, Argentina in a 5-year-old female poodle dog. The dog exhibited ocular signs of uveitis and lymphadenitis. To reach a clinical and etiological diagnosis, imaging studies, routine laboratory tests and serological tests were performed. A mycological analysis was conducted on the material obtained by puncturing three lymph nodes. Additionally, morphological, metabolic, and molecular analyses were performed. Antifungal susceptibility testing was also conducted using broth microdilution and diffusion methods. Phenotypic, metabolic, and sequencing techniques identified the isolated organism as P. wickerhamii. This isolate displayed susceptibility to amphotericin, variable susceptibility to itraconazole and voriconazole, and resistance to fluconazole and caspofungin. The frequent presence of pets in our homes highlights the need for a more comprehensive diagnostic approach. This is important because, from a public health perspective, dogs could serve as indicators of algal presence in the environments they frequently share with humans.Ítem Acceso Abierto First total synthesis of chromanone A, preparation of related compounds and evaluation of their antifungal activity against Candida albicans, a biofilm forming agent(Royal Society of Chemistry, 2021-06-01) Cortés, Iván; Cordisco, Estefanía; Kaufman, Teodoro Saúl ; Sortino, Maximiliano Andrés; Svetaz, Laura Andrea; Bracca, Andrea Beatriz Juana; https://orcid.org/0000-0002-8069-2793; https://orcid.org/0000-0002-6574-1702; https://orcid.org/0000-0003-3173-2178; https://orcid.org/0000-0002-4271-1690; https://orcid.org/0000-0002-1023-1641; https://orcid.org/0000-0003-2647-475XA straightforward and convenient approach for the first total syntheses of chromanone A and a related 7-OMe substituted natural product is reported. These unique C-3 substituted 2-hydroxymethyl chromones were recently isolated as fungal metabolites. Chromanone A was synthesized in 25.3% overall yield from the readily available pyrocatechol, whereas the second natural product was prepared in 39.7% global yield. A small library of chromones, including both natural products and some of their synthetic heterocyclic precursors, was evaluated against Candida albicans ATCC 10231, a biofilm forming agent. It was found that 8-methoxy-3-methyl-4-oxo-4H-chromene-2-carbaldehyde, a partially oxidized form of chromanone A, exhibited a minimum inhibitory concentration of 7.8 μg mL−1 and significantly inhibited the yeast's virulence factors, including the adherence to buccal epithelial cells and the secretion of phospholipases, as well as the formation of germ tubes and the generation of the hyphal pseudomycelium. In addition, despite the heterocycle exhibiting non-significant inhibition of the formation of the Candida biofilm, it completely inhibited the growth of C. albicans in preformed biofilms at 62.5 μg mL−1.Ítem Acceso Abierto Hybrid molecules containing a 7-chloro-4-aminoquinoline nucleus and a substituted 2-Pyrazoline with antiproliferative and antifungal activity(MDPI, 2016-07-27) Montoya, Alba; Quiroga, Jairo; Abonia, Rodrigo; Derita, Marcos Gabriel; Sortino, Maximiliano Andrés ; Ornelas, Alfredo; Zacchino, Susana; Insuasty, BraulioÍtem Acceso Abierto Larrea nitida extract-loaded nanodispersions as a novel bio-stimulant for tomato plants(Elsevier, 2024-12-05) Rocha, Felipe; Svetaz, Laura Andrea; Sortino, Maximiliano Andrés; Campos Bermúdez, Valeria Alina; Rius, Sebastián PabloLarrea nitida Cav. (Zygophyllaceae) hydrophobic extract (LE) is rich in antimicrobial and antioxidant compounds. In our previous study, water-soluble nanodispersions without (PZ) and with LE (PZLE) were produced to facilitate their application in agriculture. The foliar treatment was carried out with water (control), PZ and PZLE thrice a week at concentrations of 33 and 100 mg.L− 1 on 1-week-old tomato seedlings (Solanum lycopersicum L. variety perita platensis). PZLE at a concentration of 100 mg.L− 1 significantly induced a growth promotion effect and decreased the activity of the antioxidant enzymes guaiacol peroxidase (GPx) and catalase (CAT), probably due to the presence of antioxidant compounds in PZLE. However, 5 days after infection with Pseudomona syringae pv. tomato, the activity of CAT increased by 73 % compared to the control, as a response to the stress caused by the infection. Additionally, plants treated with PZLE at 33 and 100 mg.L− 1 exhibited reductions in infection symptoms of 44 % and 76 %, respectively. As for both concentrations of PZ, no significant differences were found when compared to the control, suggesting a protective effect of PZLE. The photosynthetic parameters of the plants, such as Phi2 (φPSII), non-photochemical quenching (NPQ) and the relative chlorophyll in the leaves of these plants remained unaffected, suggesting no detrimental effects of PZLE on photosynthetic efficiency. PZLE demonstrates potential as a bio-stimulant for tomato plants, offering a complementary approach to traditional agricultural inputs.Ítem Acceso Abierto Miconazole Nitrate Microparticles in Lidocaine Loaded Films as a treatment for Oropharyngeal Candidiasis(MDPI, 2023-05-07) Tejada, Guillermo; Calvo, Natalia Lorena; Morri, Mauro; Sortino, Maximiliano Andrés; Lamas, María Celina; Alvarez, Vera A.; Leonardi, Darío; https://orcid.org/0000-0002-4457-9099; https://orcid.org/0000-0003-1099-3686; https://orcid.org/0000-0002-4271-1690; https://orcid.org/0000-0002-4909-4592; https://orcid.org/0000-0003-2292-3570Oral candidiasis is an opportunistic infection that affects mainly individuals with weakened immune system. Devices used in the oral area to treat this condition include buccal films, which present advantages over both oral tablets and gels. Since candidiasis causes pain, burning, and itching, the purpose of this work was to develop buccal films loaded with both lidocaine (anesthetic) and miconazole nitrate (MN, antifungal) to treat this pathology topically. MN was loaded in microparticles based on different natural polymers, and then, these microparticles were loaded in hydroxypropyl methylcellulose-gelatin-based films containing lidocaine. All developed films showed adequate adhesiveness and thickness. DSC and XRD tests suggested that the drugs were in an amorphous state in the therapeutic systems. Microparticles based on chitosan-alginate showed the highest MN encapsulation. Among the films, those containing the mentioned microparticles presented the highest tensile strength and the lowest elongation at break, possibly due to the strong interactions between both polymers. These films allowed a fast release of lidocaine and a controlled release of MN. Due to the latter, these systems showed antifungal activity for 24 h. Therefore, the treatment of oropharyngeal candidiasis with these films could reduce the number of daily applications with respect to conventional treatments.Ítem Acceso Abierto Optimización de variables en ensayos de actividad antifúngica fotodinámica frente a especies de Candida(Asociación Argentina de Microbiología, 2021-12) Bulacio, Lucía; Ramadán, Silvana; Dalmaso, Hernán; Luque, Alicia Graciela; Sortino, Maximiliano AndrésLas infecciones orales causadas por levaduras del género Candida son muy comunes en pacientes con factores predisponentes, ya sea por estados fisiológicos o ciertas patologías de base. Estos cuadros pueden, además, evolucionar hacia formas diseminadas. En este trabajo se evaluaron in vitro algunos protocolos de terapia antifúngica fotodinámica contra levaduras del género Candida, para establecer las condiciones óptimas de radiación luego de aplicar compuestos fotosensibilizantes. Se evaluaron 39 cepas de distintas especies de Candida, que se expusieron a 12 colorantes, 8 fuentes de radiación y 3 tiempos de exposición. El azul de toluidina combinado con la exposición a luz proveniente de lámpara de diodo emisor de luz (LED) tipo reflector de 20 W durante 60 minutos mostró una buena actividad fotodinámica. Dadas las desventajas asociadas al uso de antifúngicos convencionales, como la aparición de cepas resistentes, de recidivas y de efectos adversos, la terapia antifúngica fotodinámica es una estrategia promisoria para el tratamiento de infecciones localizadasÍtem Acceso Abierto Prevalence of Malassezia species in patients with pityriasis versicolor in Rosario, Argentina(Elsevier España, 2011-03-17) Ramadán, Silvana; Sortino, Maximiliano Andrés ; Bulacio, Lucía; Marozzi, María Laura; López, Clara; Ramos, LauraBackground Malassezia species are considered opportunistic yeasts of increasing clinical importance. These lipophilic yeasts are associated with various human diseases, especially pityriasis versicolor (PV), a chronic superficial scaling dermatomycosis. Aims The aim of this study was to isolate, identify and analyze the distribution of the different species of Malassezia in patients with PV in Rosario city (Argentina). Methods A total of 264 clinical samples were studied. Isolates were identified on the basis of microscopic observation of cells, and physiological properties, such as the presence of catalase, ability to use Tween compounds, splitting of esculin, and morphology, color and precipitate production on chromogenic agar CHROMagar-Malassezia medium (CHROMM). Results The highest prevalence of PV in this study was observed in the 25- to 45-year-old group. No differences were found in the development of PV between sexes. The most affected areas of body were the trunk and face. Malassezia sympodialis (51%) was the most commonly isolated species, followed in frequency by M. globosa (40%), Malassezia furfur (7%), Malassezia obtusa (1%) and Malassezia slooffiae (1%). Conclusions The success for a correct identification of these yeasts is important to improve our knowledge about their epidemiological role in PV and also to detect the appearance of strains which are resistant to the commonly used antifungal drugs.Ítem Acceso Abierto Solvent-free microwave-assisted synthesis of novel pyrazolo[40 ,30 :5,6]pyrido[2,3-d]pyrimidines with potential antifungal activity(Elsevier, 2015-03-17) Acosta, Paola; Insuasty, Braulio; Ortiz, Alejandro; Abonia, Rodrigo; Sortino, Maximiliano Andrés ; Zacchino, Susana; Quiroga, JairoÍtem Acceso Abierto Synergistic effects of Thymus vulgaris essential oil in combination with antifungal agents and inhibition of virulence factors of Candida albicans(Elsevier, 2023-08-29) Butassi, Estefanía; Blanc, Alan Roy; Sortino, Maximiliano Andrés; Svetaz, Laura Andrea; https://orcid.org/0000-0002-4271-1690; https://orcid.org/0000-0002-1023-1641Background: Combination antifungal therapy has become a prominent approach in medical practice as it takes advantage of synergistic interactions by interfering with multiple targets of the pathogen, broadening the spectrum of activity, reducing the development of resistance, and improving treatment outcomes. Therefore, combining conventional antifungal drugs with natural products can increase antifungal activity, reduce side effects, and optimize therapeutic effects. Purpose: The present study aimed to evaluate the antifungal activity of thyme essential oil (ThyEO) in combination with amphotericin B, caspofungin, fluconazole, itraconazole, and posaconazole (PSZ), as well as its inhibitory effect on Candida albicans virulence factors. Materials and Methods: The microbroth dilution assay was employed to determine the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC). Interactions were assessed using the microdilution checkerboard assay. Ergosterol and methylene blue assays were used to detect effects on fungal membrane, while the sorbitol assay was used to detect effects on fungal cell wall. Inhibition of yeast virulence factors (adherence to epithelial cells, germ tube and pseudomycelium formation, secretion of hydrolytic enzymes, and biofilm formation) was assessed with previously reported methods. Results: Almost all combinations showed additivism against C. albicans, except ThyEO/PSZ (31.25/0.0039 µg/ml), which showed partial synergism. Furthermore, all mixtures were fungicidal against C. albicans strains. ThyEO/PSZ, its components alone, and thymol were shown to disrupt the fungal cytoplasmic membrane, increasing its permeability. ThyEO/PSZ, at sub-inhibitory concentrations, significantly decreased the ability of C. albicans to adhere to buccal epithelial cells. ThyEO/PSZ, ThyEO, and PSZ were able to reduce the pseudomycelium production of C. albicans while thymol completely inhibited its formation. ThyEO/PSZ, each combination component on its own, and thymol inhibited biofilm formation and preformed biofilm of C. albicans. Notably, ThyEO/PSZ showed synergistic and fungicidal activity against a resistant strain of C. albicans, reducing the PSZ dose by 4-fold. Conclusion: These findings make ThyEO and ThyEO/PSZ mixture valuable candidates for the development of alternative antifungals with a lower incidence of adverse effects.Ítem Acceso Abierto Synthesis and DFT calculations of novel vanillin-chalcones and their 3-aryl-5-(4-(2- (dimethylamino)- ethoxy)-3-methoxyphenyl)- 4,5-dihydro-1H-pyrazole-1-carbaldehyde derivatives as antifungal agents(MDPI, 2017-09-05) Illicachi, Luis Alberto; Montalvo-Acosta, Joel José; Insuasty, Alberto; Quiroga, Jairo; Abonia, Rodrigo; Sortino, Maximiliano Andrés ; Zacchino, Susana; Insuasty, BraulioÍtem Acceso Abierto Synthesis of Novel Triazine-Based Chalcones and 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines as Potential Leads in the Search of Anticancer, Antibacterial and Antifungal Agents(MDPI, 2024-03-23) Moreno, Leydi M.; Quiroga, Jairo; Abonia, Rodrigo; Crespo Ortíz, María del Pilar; Aranaga, Carlos Andrés; Martínez-Martínez, Luis; Sortino, Maximiliano Andrés; Barreto, Mauricio; Burbano, María E.; Insuasty, Braulio; https://orcid.org/0000-0002-9451-3063; https://orcid.org/0000-0003-3256-0961; https://orcid.org/0000-0003-2160-5167; https://orcid.org/0000-0003-1806-657X; https://orcid.org/0000-0002-6091-4045; https://orcid.org/0000-0002-4271-1690; https://orcid.org/0000-0001-5361-4901; https://orcid.org/0000-0001-8371-3310This study presents the synthesis of four series of novel hybrid chalcones (20,21)a–g and (23,24)a–g and six series of 1,3,5-triazine-based pyrimido[4,5-b][1,4]diazepines (28–33)a–g and the evaluation of their anticancer, antibacterial, antifungal, and cytotoxic properties. Chalcones 20b,d, 21a,b,d, 23a,d–g, 24a–g and the pyrimido[4,5-b][1,4]diazepines 29e,g, 30g, 31a,b,e–g, 33a,b,e–g exhibited outstanding anticancer activity against a panel of 60 cancer cell lines with GI50 values between 0.01 and 100 μM and LC50 values in the range of 4.09 μM to >100 μM, several of such derivatives showing higher activity than the standard drug 5-fluorouracil (5-FU). On the other hand, among the synthesized compounds, the best antibacterial properties against N. gonorrhoeae, S. aureus (ATCC 43300), and M. tuberculosis were exhibited by the pyrimido[4,5-b][1,4]diazepines (MICs: 0.25–62.5 µg/mL). The antifungal activity studies showed that triazinylamino-chalcone 29e and triazinyloxy-chalcone 31g were the most active compounds against T. rubrum and T. mentagrophytes and A. fumigatus, respectively (MICs = 62.5 μg/mL). Hemolytic activity studies and in silico toxicity analysis demonstrated that most of the compounds are safe.Ítem Acceso Abierto Water extract from inflorescences of industrial hemp Futura 75 variety as a source of anti-inflammatory, anti-proliferative and antimycotic agents: results from in silico, in vitro and ex vivo studies(MDPI, 2020-05-17) Orlando, Giustino; Recinella, Lucia; Chiavaroli, Annalisa; Brunetti, Luigi; Leone, Sheila; Carradori, Simone; Di Simone, Simonetta; Ciferri, Maria Chiara; Zengin, Gokhan; Ak, Gunes; Abdullah, Hassan H.; Cordisco, Estefanía; Sortino, Maximiliano Andrés; Svetaz, Laura Andrea; Politi, Matteo; Angelini, Paola; Covino, Stefano; Venanzoni, Roberto; Cesa, Stefania; Menghini, Luigi; Ferrante, ClaudioIndustrial hemp (Cannabis sativa) is traditionally cultivated as a valuable source of fibers and nutrients. Multiple studies also demonstrated antimicrobial, anti-proliferative, phytotoxic and insecticide effects of the essential oil from hemp female inflorescences. On the other side, only a few studies explored the potential pharmacological application of polar extracts from inflorescences. In the present study, we investigated the water extract from inflorescences of industrial hemp Futura 75 variety, from phytochemical and pharmacological point of view. The water extract was assayed for phenolic compound content, radical scavenger/reducing, chelating and anti-tyrosinase effects. Through an ex vivo model of toxicity induced by lipopolysaccharide (LPS) on isolated rat colon and liver, we explored the extract effects on serotonin, dopamine and kynurenine pathways and the production of prostaglandin (PG)E2. Anti-proliferative effects were also evaluated against human colon cancer HCT116 cell line. Additionally, antimycotic effects were investigated against Trichophyton rubrum, Trichophyton interdigitale, Microsporum gypseum. Finally, in silico studies, including bioinformatics, network pharmacology and docking approaches were conducted in order to predict the putative targets underlying the observed pharmacological and microbiological effects. Futura 75 water extract was able to blunt LPS-induced reduction of serotonin and increase of dopamine and kynurenine turnover, in rat colon. Additionally, the reduction of PGE2 levels was observed in both colon and liver specimens, as well. The extract inhibited the HCT116 cell viability, the growth of T. rubrum and T. interdigitale and the activity of tyrosinase, in vitro, whereas in silico studies highlighting the inhibitions of cyclooxygenase-1 (induced by carvacrol), carbonic anhydrase IX (induced by chlorogenic acid and gallic acid) and lanosterol 14-α-demethylase (induced by rutin) further support the observed pharmacological and antimycotic effects. The present findings suggest female inflorescences from industrial hemp as high quality by-products, thus representing promising sources of nutraceuticals and cosmeceuticals against inflammatory and infectious diseases.