Estudio de tagetes minuta L. como fuente de moléculas fotosensibilizantes para aplicación en quimioterapia antifúngica fotodinámica

Las infecciones fúngicas, como la candidiasis, se han vuelto frecuentes en pacientes inmuno comprometidos y su tratamiento se dificulta debido al bajo número de antifúngicos disponibles y sus desventajas: toxicidad, generación de resistencia y alto costo. Una de las alternativas es la Quimioterapia Fotodinámica Antimicrobiana (QTFA), que utiliza compuestos fotosensibilizantes (CF) y luz de una determinada longitud de onda para inducir un daño oxidativo en patógenos microbianos. Debido a que se ha reportado la presencia de CF en las especies del género Tagetes, se postuló como objetivo de este trabajo, obtener distintos extractos de Tagetes minuta para evaluar su actividad antifúngica frente a cinco especies del género Candida. 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. Se observó inhibición de la formación de tubo germinativo y disminución en la adherencia a células epiteliales, como también acción antifúngica contra biofilm. La baja concentración de los extractos seleccionados 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 los tratamientos de candidiasis utilizando la terapia fotodinámica.Fil: Giacone, Lucía. Universidad Nacional de RosarioFil: Cordisco, Estefanía. Universidad Nacional de RosarioFil: Sortino, Maximiliano. Universidad Nacional de Rosari

Evaluation of the antifungal photodynamic activity of Thymophylla pentachaeta extracts against Candida albicans and its virulence factors

Background: Candida albicans is one of the most common causative of opportunistic infections. Treatment of candidiasis is challenging considering the few antifungal drugs available and the increase in resistance. Antimicrobial photodynamic therapy (aPDT) is a recently developed therapeutic option that combines a non-toxic photosensitizer (PS) and light to kill the microbial pathogens. Targeting virulence, defined as the ability of a pathogen to cause overt disease, represents another attractive target for the development of novel antifungal agents. Thymophylla pentachaeta (DC.) Small var. belenidium (DC.) is an endemic plant from Argentina in which the presence of thiophenes, biologically active compounds whose antifungal activity is enhanced by irradiation with Ultraviolet A (UVA), have been already described. Purpose: The purpose of this study was to evaluate the photodynamic antifungal activity of hexane (Hex), dichloromethane (DCM), ethyl acetate (EtOAc) and methanol (MeOH) extracts from T. pentachaeta var. belenidium and their inhibitory effects on C. albicans virulence factors as well as biofilm formation and eradication. Study Design/Methods: Antifungal photodynamic activity of Hex, DCM, EtOAc and MeOH extracts from different parts of the plant were assessed with the microbroth dilution, bioautography and the time-kill assays, under light and darkness conditions. The capacities of the most active extracts of inhibiting Candida virulence factors (adherence to epithelial cells, germ tube and pseudomycelium formation and hydrolytic enzyme secretion) were assessed. In addition, the activity against biofilm formation and eradication has been investigated by reaction with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) that quantifies living cells in these structures. Results: Hex and DCM extracts from T. pentachaeta roots exhibited high photodynamic antifungal activity against C. albicans [Minimal fungicide concentrations (MFCs)= 7.8 µg/ml] under UVA light irradiation. Chemical analysis of active extracts (Hex and DCM from roots) revealed the presence of photoactive thiophenes. Both extracts generate reactive oxygen species through type I and II mechanisms. These extracts, at sub-inhibitory concentrations, under light conditions decreased the adherence of C. albicans to Buccal Epithelial Cells (BEC), inhibited germ tube formation and reduced esterase production. Finally, they demonstrated activity against preformed biofilms submitted to irradiation (MFCs= 3.91 µg/ml and 15.63 µg/ml for Hex and DCM extracts, respectively). Conclusion: Taking together, results demonstrated the strong photodynamic effects of T. pentachaeta root extracts under UVA irradiation, making them valuable alternatives to the already established antifungal drugs against C. albicans.Fil: Cordisco, Estefanía. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Petenatti, Elisa Margarita. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; ArgentinaFil: Svetaz, Laura Andrea. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Sortino, Maximiliano Andrés. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentin

Aqueous micellar two-phase system as an alternative method to selectively remove soy antinutritional factors

In this work, different antinutritional factors (trypsin inhibitors, isoflavones and raffinose family oligosaccharides) were selectively removed from soy flour by using aqueous micellar two-phase systems (AMTPS). The effects of independent variables including temperature (30–60 °C), time (10–40 min) and solid to liquid ratio (0.025–0.050 g/L) on the extraction of each antinutritional factor were analyzed using a full factorial design. As general tendency, temperature and time were the most significant parameters (p < 0.05). The best condition for the selective recovery (97% of isoflavones at top phase, and more than 50% of the rest of ANFs at bottom phase) were 5 g/L of Genapol X-080, 0.2 moL/L of sodium citrate pH 5.00, 30 °C, 40 min and 0.050 g/L. Besides, in vitro gastrointestinal digestions assays demonstrated that the treated soy flour improved its protein digestibility. The findings of this work represent the introduction of a novel methodology to selectively remove soy antinutritional factors.Fil: Haidar, Carla Nahir. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Procesos Biotecnológicos y Químicos Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Procesos Biotecnológicos y Químicos Rosario; ArgentinaFil: Coscueta, Ezequiel Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Procesos Biotecnológicos y Químicos Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Procesos Biotecnológicos y Químicos Rosario; ArgentinaFil: Cordisco, Estefanía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Procesos Biotecnológicos y Químicos Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Procesos Biotecnológicos y Químicos Rosario; ArgentinaFil: Nerli, Bibiana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Procesos Biotecnológicos y Químicos Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Procesos Biotecnológicos y Químicos Rosario; ArgentinaFil: Pellegrini Malpiedi, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Procesos Biotecnológicos y Químicos Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Procesos Biotecnológicos y Químicos Rosario; Argentin

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

Industrial 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.Fil: Orlando, Giustino. University “G. d’Annunzio”. Department of Pharmacy; ItaliaFil: Recinella, Lucia. University “G. d’Annunzio”. Department of Pharmacy; ItaliaFil: Chiavaroli, Annalisa. University “G. d’Annunzio”. Department of Pharmacy; ItaliaFil: Brunetti, Luigi. University “G. d’Annunzio”. Department of Pharmacy; ItaliaFil: Leone, Sheila. University “G. d’Annunzio”. Department of Pharmacy; ItaliaFil: Carradori, Simone. University “G. d’Annunzio”. Department of Pharmacy; ItaliaFil: Di Simone, Simonetta. University “G. d’Annunzio”. Department of Pharmacy; ItaliaFil: Ciferri, Maria Chiara. University “G. d’Annunzio”. Department of Pharmacy; ItaliaFil: Zengin, Gokhan. Universidad de Selcuk; TurquíaFil: Ak, Gunes. Universidad de Selcuk; TurquíaFil: Abdullah, Hassan H.. Salahaddin University-Erbil; Iraq. Universiti Sains Malaysia; MalasiaFil: Cordisco, Estefanía. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Sortino, Maximiliano Andrés. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Svetaz, Laura Andrea. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Politi, Matteo. University “G. d’Annunzio”. Department of Pharmacy; ItaliaFil: Angelini, Paola. Università di Perugia; ItaliaFil: Covino, Stefano. Università di Perugia; ItaliaFil: Venanzoni, Roberto. Università di Perugia; ItaliaFil: Cesa, Stefania. Università degli Studi di Roma "La Sapienza"; ItaliaFil: Menghini, Luigi. University “G. d’Annunzio”. Department of Pharmacy; ItaliaFil: Ferrante, Claudio. University “G. d’Annunzio”. Department of Pharmacy; Itali

Desarrollo de fitomedicinas antifúngicas a partir de plantas de la flora argentina

Las 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.Fil: Cordisco, Estefanía. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Área Farmacognosia; Argentina

Hybrid combinations containing natural products and antimicrobial drugs that interfere with bacterial and fungal biofilms

Background: Biofilms contribute to the pathogenesis of many chronic and difficult-to eradicate infections whose treatment is complicated due to the intrinsic resistance to conventional antibiotics. As a consequence, there is an urgent need for strategies that can be used for the prevention and treatment of biofilm-associated infections. The combination therapy comprising an antimicrobial drug with a low molecular weight (MW) natural product and an antimicrobial drug (antifungal or antibacterial) appeared as a good alternative to eradicate biofilms. Purpose: The aims of this review were to perform a literature search on the different natural products that have showed the ability of potentiating the antibiofilm capacity of antimicrobial drugs, to analyze which are the antimicrobial drugs most used in combination, and to have a look on the microbial species most used to prepare biofilms. Results: Seventeen papers, nine on combinations against antifungal biofilms and eight against antibacterial biofilms were collected. Within the text, the following topics have been developed: breaf history of the discovery of biofilms; stages in the development of a biofilm; the most used methodologies to assess antibiofilm-activity; the natural products with capacity of eradicating biofilms when acting alone; the combinations of low MW natural products with antibiotics or antifungal drugs as a strategy for eradicating microbial biofilms and a list of the low MW natural products that potentiate the inhibition capacity of antifungal and antibacterial drugs against biofilms. Conclusions and perspectives: Regarding combinations against antifungal biofilms, eight over the nine collected works were carried out with in vitro studies while only one was performed with in vivo assays by using Caenorhabditis elegans nematode. All studies use biofilms of the Candida genus. A 67% of the potentiators were monoterpenes and sesquiterpenes and six over the nine works used FCZ as the antifungal drug. The activity of AmpB and Caspo was enhanced in one and two works respectively. Regarding combinations against bacterial biofilms, in vitro studies were performed in all works by using several different methods of higher variety than the used against fungal biofilms. Biofilms of both the gram (+) and gram (-) bacteria were prepared, although biofilm of Staphylococcus spp. were the most used in the collected works. Among the discovered potentiators of antibacterial drugs, 75% were terpenes, including mono, di- and triterpenes, and, among the atibacterial drugs, several structurally diverse types were used in the combinations: aminoglycosides, β-lactams, glucopeptides and fluoroquinolones. The potentiating capacity of natural products, mainly terpenes, on the antibiofilm effect of antimicrobial drugs opens a wide range of possibilities for the combination antimicrobial therapy. More in vivo studies on combinations of natural products with antimicrobial drugs acting against biofilms are highly required to cope the difficult to treat biofilm-associated infections.Fil: Zacchino, Susana Alicia Stella. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; ArgentinaFil: Butassi, Estefanía. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cordisco, Estefanía. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; ArgentinaFil: Svetaz, Laura Andrea. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Antifungal activity of traditional medicinal plants from Argentina: effect of their combination with antifungal drugs

The incidence of fungal infections has experienced a marked increase in the last two decades being limited to a few drugs with serious drawbacks. Combination therapy has emerged as an approach to improve the efficacy of currently used antifungal therapy that also may delay the evolution of resistance. The objectives of this work are to present a bibliographic search on the plants used in traditional medicine in Argentina for ailments related to fungal infections and to investigate the antifungal activity of currently used antifungal drugs in combination with natural extracts. Results of the bibliographic investigation showed that 153 species belonging to 56 families and 120 genera from Argentina are applied to treat signs and symptoms considered to maintain ethnopharmacological uses related to fungal infections, mainly for skin and mucosal conditions. Regarding the evaluation of the antifungal activity of combinations between extracts and antifungal drugs, we observed that extracts from plants species belonging to a genera traditionally used for ailments related to fungal infections have more chances of enhancing the activity of amphotericin B, fluconazole and itraconazole. In addition, we observed that there is a greater chance of finding an enhancement in the activity of the commercial antifungals when the combination is performed with extracts that have shown activity in solitary. Nevertheless, inactive extracts that would have been discarded according to the classic strategy displayed activity in combination and they continue being potential candidates in the search for new antifungals.Fil: Cordisco, Estefanía. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Sortino, Maximiliano Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; ArgentinaFil: Svetaz, Laura Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentin

Physicochemical characterization of aqueous micellar systems formed by environmentally friendly salts

In this work, environmentally friendly aqueous micellar two-phase systems containing nonionic surfactants (Triton X-114, Triton X-100 and Genapol X080) and organic salts (sodium citrate and sodium tartrate) were characterized. In order to accomplish this objective, the binodal diagrams (cloud point vs. surfactant concentration) were obtained for each condition. Additionally, critical micelle concentration (CMC) and micellar hydrodynamic diameter (DH) were determined for each system. According to the obtained results, it was found that the presence of salts lowered the CMC (ΔCMC up to 0.15 mM) and cloud point values (ΔCP up to 18 °C) following the sequence: sodium citrate > sodium tartrate. In addition, the hydrodynamic diameters of the micelles were notoriously increased in presence of the studied salts, showing the high sensitivity of the described aqueous micellar two-phase systems to the medium condition. These results open perspectives for the use of greener aqueous micellar two-phase systems for bioseparation purposes.Fil: Cordisco, Estefanía. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Rosario. Instituto de Procesos Biotecnologicos y Quimicos Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; ArgentinaFil: Haidar, Carla. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Rosario. Instituto de Procesos Biotecnologicos y Quimicos Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; ArgentinaFil: Goñi, Rocío. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Rosario. Instituto de Procesos Biotecnologicos y Quimicos Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; ArgentinaFil: Nerli, Bibiana Beatriz. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Rosario. Instituto de Procesos Biotecnologicos y Quimicos Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; ArgentinaFil: Pellegrini Malpiedi, Luciana. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Rosario. Instituto de Procesos Biotecnologicos y Quimicos Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentin

Photodynamic activity of Tagetes minuta extracts against superficial fungal infections

Candida and dermatophyte species are the most common causes of superficialmycoses because their treatment can be difficult due to limitations of current antifungal drugs in terms of toxicity, bioavailability, interactions, narrow-spectrum activity, and development of resistance. Photodynamic therapy (PDT) involves the topical administration of a photosensitizer in combination with light of an appropriate wavelength and molecular oxygen that produces reactive oxygen species (ROS), which promote damage to several vital components of the microorganism. Tagetes species are known as a source of thiophenes, biologically active compounds whose antifungal activity is enhanced by irradiation with UVA. The present investigation evaluated Tagetes minuta extracts as a photosensitizer on growth of Candida and dermatophytes and their effect on Candida virulence factors. T. minuta root hexane and dichloromethane extracts demonstrated high photodynamic antifungal activity. Bioautographic assays and chromatographic analysis revealed the presence of five thiophenes with reported photodynamic antifungal activities under UVA. Analysis of ROS production indicated that both type I and II reactions were involved in the activity of the extracts. In addition, the extracts inhibited virulence factors of Candida, such as adherence to epithelial surfaces and germ tube formation and showed efficacy against different Candida morphologies: Budding cells, cells with germ tube and biofilms. Results suggested that PDT with T. minuta extracts might become a valuable alternative to the already established antifungal drugs for the treatment of superficial fungal infections.Fil: Giacone, Lucía. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; ArgentinaFil: Cordisco, Estefanía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; ArgentinaFil: Garrido, María Clara. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; ArgentinaFil: Petenatti, Elisa Margarita. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; ArgentinaFil: Sortino, Maximiliano Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentin

First total synthesis of chromanone A, preparation of related compounds and evaluation of their antifungal activity against Candida albicans, a biofilm forming agent

A 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.Fil: Cortés, Iván. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Cordisco, Estefanía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; ArgentinaFil: Kaufman, Teodoro Saul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; ArgentinaFil: Sortino, Maximiliano Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; ArgentinaFil: Svetaz, Laura Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Bracca, Andrea Beatriz Juana. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentin