Synthesis and biological evaluation of 1-alkylaminomethyl-1,1-bisphosphonic acids against Trypanosoma cruzi and Toxoplasma gondii

As an extension of our project aimed at the search for new chemotherapeutic agents against Chagas disease and toxoplasmosis, several 1,1-bisphosphonates were designed, synthesized and biologically evaluated against Trypanosoma cruzi and Toxoplasma gondii, the etiologic agents of these diseases, respectively. In particular, and based on the antiparasitic activity exhibited by 2-alkylaminoethyl-1,1-bisphosphonates targeting farnesyl diphosphate synthase, a series of linear 2-alkylaminomethyl-1,1-bisphosphonic acids (compounds 21–33), that is, the position of the amino group was one carbon closer to the gem-phosphonate moiety, were evaluated as growth inhibitors against the clinically more relevant dividing form (amastigotes) of T. cruzi. Although all of these compounds resulted to be devoid of antiparasitic activity, these results were valuable for a rigorous SAR study. In addition, unexpectedly, the synthetic designed 2-cycloalkylaminoethyl-1,1-bisphosphonic acids 47–49 were free of antiparasitic activity. Moreover, long chain sulfur-containing 1,1-bisphosphonic acids, such as compounds 54–56, 59, turned out to be nanomolar growth inhibitors of tachyzoites of T. gondii. As many bisphosphonate-containing molecules are FDA-approved drugs for the treatment of bone resorption disorders, their potential nontoxicity makes them good candidates to control American trypanosomiasis and toxoplasmosis.Fil: Galaka, Tamila Pavlivna. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; ArgentinaFil: Falcone, Bruno Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; ArgentinaFil: Li, Catherine. University of Georgia; Estados UnidosFil: Szajnman, Sergio Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; ArgentinaFil: Moreno, Silvia N.J.. University of Georgia; Estados UnidosFil: Docampo, Roberto. University of Georgia; Estados UnidosFil: Rodriguez, Juan Bautista. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentin

Aryloxyethyl thiocyanates are potent growth inhibitors of Trypanosoma cruzi and Toxoplasma gondii

As a part of our project aimed at searching new safe chemotherapeutic agents against parasitic diseases, several compounds structurally related to the antiparasitic agent WC-9 (4-phenoxyphenoxyethyl thiocyanate), which were modified at the terminal phenyl ring, were designed, synthesized and evaluated as growth inhibitors against Trypanosoma cruzi, the etiological agent of Chagas disease and Toxoplasma gondii, the parasite responsible of toxoplasmosis. Most of the synthetic analogues exhibited similar antiparasitic activity being slightly more potent than our lead WC-9. For example, the trifluoromethyl derivatives 15 and 16 exhibited ED50 values of 10.0 uM and 9.2 uM, respectively, against intracellular T. cruzi, whereas they showed potent action against tachyzoites of T. gondii (ED50 values 1.6 uM and 1.9 uM against T. gondii, respectively). In addition, the WC-9 analogues 48 and 61, in which the terminal aryl group was meta with respect to the alkyl chain bearing the thiocyanate group, showed potent inhibitory action against both T. cruzi and T. gondii at the very low micromolar range suggesting that para-phenyl substitution pattern is not necessarily required for biological activity.Fil: Chao, Maria Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; ArgentinaFil: Exeni Matiuzzi, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; ArgentinaFil: Storey, Melissa. University of Georgia; Estados UnidosFil: Li, Catherine. University of Georgia; Estados UnidosFil: Szajnman, Sergio Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; ArgentinaFil: Docampo, Roberto. University of Georgia; Estados UnidosFil: Moreno, Silvia N. J.. University of Georgia; Estados UnidosFil: Rodriguez, Juan Bautista. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentin

Bean yellow mosaic virus infecting broad bean in the green belt of Córdoba, Argentina

Broad bean (Vicia faba L) is the fourth most important pulse crop in the world. In Argentina, broad bean production was of 1,841 hectares and 16,500 tons during the 2017 growing season. Broad bean is commonly used in rotations; especially by farmers located in “green belts” that are peri-urban areas surrounding large cities that include horticultural family farms. Plants showing marked foliar mosaic symptoms, typical of viral infection, were collected during the 2015 growing season in the green belt of Córdoba city, Argentina. Preparations of symptomatic tissues were mechanically inoculated onto healthy broad bean plants in the greenhouse, which developed symptoms similar to those observed in the field. In addition, symptomatic samples were positive when tested by indirect ELISA with the anti-potyvirus group monoclonal antibody. Further, flexuous filamentous particles typical of potyviruses were observed under the electronic microscope on dip preparations. Lastly, total RNA was extracted from a symptomatic leaf and high-throughput sequenced, which allowed the assembly of a single virus sequence corresponding to a new highly divergent strain of Bean yellow mosaic virus (BYMV). Phylogenetic insights clustered this Argentinean broad bean isolate (BYMV-ARGbb) within group IX of BYMV. Given the economical importance of this virus and its associated disease, the results presented here are a pivotal first step oriented to explore the eventual incidence and epidemiological parameters of BYMV in broad bean in Argentina.Instituto de Patología VegetalFil: Rodriguez Pardina, Patricia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patología Vegetal; ArgentinaFil: Nome Docampo, Claudia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patología Vegetal; ArgentinaFil: Reyna, Pablo Gastón. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET); ArgentinaFil: Reyna, Pablo Gastón. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patología Vegetal; ArgentinaFil: Muñoz, Nacira Belén. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Fisiología y Recursos Genéticos Vegetales; ArgentinaFil: Muñoz, Nacira Belén. Universidad Nacional de Córdoba (UNC). Facultad de Ciencias Exactas Físicas y Naturales (FCEFyN).Cátedra de Fisiología Vegetal; ArgentinaFil: Arguello Caro, Evangelina Beatriz. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patología Vegetal; ArgentinaFil: Arguello Caro, Evangelina Beatriz. Universidad Nacional de Córdoba (UNC). Facultad de Ciencias Agropecuarias (FCA). Cátedra de Zoología Agrícola,; ArgentinaFil: Luque, Andres Vicente. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET); ArgentinaFil: Luque, Andres Vicente. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patología Vegetal; ArgentinaFil: Debat, Humberto Julio. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patología Vegetal; Argentin

Above-ground biomass estimation of arable crops using UAV-based SfM photogrammetry

This is an Accepted Manuscript of an article published by Taylor & Francis in Geocarto International on 3 dec 2018, available online: http://www.tandfonline.com/10.1080/10106049.2018.1552322Methods of estimating the total amount of above-ground biomass (AGB) in crop fields are generally based on labourious, random, and destructive in situ sampling. This study proposes a methodology for estimating herbaceous crop biomass using conventional optical cameras and structure from motion (SfM) photogrammetry. The proposed method is based on the determination of volumes according to the difference between a digital terrain model (DTM) and digital surface model (DSM) of vegetative cover. A density factor was calibrated based on a subset of destructive random samples to relate the volume and biomass and efficiently quantify the total AGB. In all cases, RMSE Z values less than 0.23 m were obtained for the DTMDSM coupling. Biomass field data confirmed the goodness of fit of the yieldbiomass estimation (R2=0,88 and 1,12 kg/ha) mainly in plots with uniform vegetation coverage. Furthermore, the method was demonstrated to be scalable to multiple platform types and sensorsThis work was supported by the life project “Operation CO2: Integrated Agroforestry Practices and Nature Conservation Against Climate Change - LIFE+ 11 ENV/ES/535” and by Xunta de Galicia under the grant “Financial aid for the consolidation and structure of competitive units of investigation in the universities of the University Galician System (2016-18)” Ref. ED431B 2016/030 and Ref. ED341D R2016/023.S

Plant survival monitoring with UAVs and multispectral data in difficult access afforested areas

This is an Accepted Manuscript of an article published by Taylor & Francis in Geocarto International on 02 Oct 2018, available online: http://www.tandfonline.com/10.1080/10106049.2018.1508312Water supply devices enable afforestation in dry climates and on poor lands with generally high success rates. Previous survival analyses have been based on the direct observation of each individual plant in the field, which entails considerable effort and costs. This study provides a low-cost method to discriminate between live and dead plants in afforestations that can efficiently replace traditional field inspections through the use of UAVs equipped with RGB and NIR sensors. The method combines the use of a conventional camera with an identical camera modified to record the NIR channel. Survival analysis was performed with digital image processing techniques based on calculated indices associated with plant vigour and PCA-based decorrelation. The method yielded results with high global accuracy rates (~96.2%) with a minimum percentage of doubtful plants, even in young plantations (seedlings < 30 cm tall). The procedure could be particularly useful in hazardous areasThis work was supported by the Xunta de Galicia under the Grant “Financial aid for the consolidation and structure of competitive units of investigation in the universities of the University Galician System (2016-18)” [ED431B 2016/030, ED341D R2016/023] and the European Program Life+ [LIFE/ENV/ES/000447] “The Green Deserts: New planting techniques for tree cultivation in desertified environments to face Climate Change”.S

Design, synthesis and biological evaluation of sulfur-containing 1,1-bisphosphonic acids as antiparasitic agents

As part of our efforts aimed at searching for new antiparasitic agents, 2-alkylmercaptoethyl-1,1-bisphosphonate derivatives were synthesized and evaluated against Trypanosoma cruzi, the etiologic agent of Chagas disease, and Toxoplasma gondii, the responsible agent for toxoplasmosis. Many of these sulfur-containing bisphosphonates were potent inhibitors against the intracellular form of T. cruzi, the clinically more relevant replicative form of this parasite, and tachyzoites of T. gondii targeting T. cruzi or T. gondii farnesyl diphosphate synthases (FPPSs), which constitute valid targets for the chemotherapy of these parasitic diseases. Interestingly, long chain length sulfur-containing bisphosphonates emerged as relevant antiparasitic agents. Taking compounds 37, 38, and 39 as representative members of this class of drugs, they exhibited ED50 values of 15.8 μM, 12.8 μM, and 22.4 μM, respectively, against amastigotes of T. cruzi. These cellular activities matched the inhibition of the enzymatic activity of the target enzyme (TcFPPS) having IC50 values of 6.4 μM, 1.7 μM, and 0.097 μM, respectively. In addition, these compounds were potent anti-Toxoplasma agents. They had ED50 values of 2.6 μM, 1.2 μM, and 1.8 μM, respectively, against T. gondii tachyzoites, while they exhibited a very potent inhibitory action against the target enzyme (TgFPPS) showing IC50 values of 0.024 μM, 0.025 μM, and 0.021 μM, respectively. Bisphosphonates bearing a sulfoxide unit at C-3 were also potent anti-Toxoplasma agents, particularly those bearing long aliphatic chains such as 43-45, which were also potent antiproliferative drugs against tachyzoites of T. gondii. These compounds inhibited the enzymatic activity of the target enzyme (TgFPPS) at the very low nanomolar range. These bisphosphonic acids have very good prospective not only as lead drugs but also as potential chemotherapeutic agents.Fil: Recher, Marion. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; ArgentinaFil: Barboza, Alejandro Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; ArgentinaFil: Li, Zhu Hong. University of Georgia; Estados UnidosFil: Galizzi, Melina. University of Georgia; Estados UnidosFil: Ferrer, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; ArgentinaFil: Szajnman, Sergio Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; ArgentinaFil: Docampo, Roberto. University of Georgia; Estados UnidosFil: Moreno, Silvia N. J.. University of Georgia; Estados UnidosFil: Rodriguez, Juan Bautista. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentin

Affinity chromatography in dynamic combinatorial libraries: one-pot amplification and isolation of a strongly binding receptor

We report the one-pot amplification and isolation of a nanomolar receptor in a multibuilding block aqueous dynamic combinatorial library using a polymer-bound template. By appropriate choice of a poly(N,N-dimethylacrylamide)-based support, unselective ion-exchange type behaviour between the oppositely charged cationic guest and polyanionic hosts was overcome, such that the selective molecular recognition arising in aqueous solution reactions is manifest also in the analogous templated solid phase DCL syntheses. The ability of a polymer bound template to identify and isolate a synthetic receptor via dynamic combinatorial chemistry was not compromised by the large size of the library, consisting of well over 140 theoretical members, demonstrating the practical advantages of a polymer-supported DCL methodology

Inorganic polyphosphate interacts with nucleolar and glycosomal proteins in trypanosomatids

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146806/1/mmi14131-sup-0001-FigS1-S9.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146806/2/mmi14131_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146806/3/mmi14131.pd

Preparation of Single-Phase Films of CH3NH3Pb(I1-xBrx)3 with Sharp Optical Band Edges.

Organometallic lead-halide perovskite-based solar cells now approach 18% efficiency. Introducing a mixture of bromide and iodide in the halide composition allows tuning of the optical bandgap. We prepare mixed bromide-iodide lead perovskite films CH3NH3Pb(I1-xBrx)3 (0 ≤ x ≤ 1) by spin-coating from solution and obtain films with monotonically varying bandgaps across the full composition range. Photothermal deflection spectroscopy, photoluminescence, and X-ray diffraction show that following suitable fabrication protocols these mixed lead-halide perovskite films form a single phase. The optical absorption edge of the pure triiodide and tribromide perovskites is sharp with Urbach energies of 15 and 23 meV, respectively, and reaches a maximum of 90 meV for CH3NH3PbI1.2Br1.8. We demonstrate a bromide-iodide lead perovskite film (CH3NH3PbI1.2Br1.8) with an optical bandgap of 1.94 eV, which is optimal for tandem cells of these materials with crystalline silicon devices.We acknowledge funding from the Engineering and Physical Sciences Research Council (EPSRC) and the Winton Programme (Cambridge) for the Physics of Sustainability. THT acknowledges funding from Cambridge Australia Scholarships and the Cambridge Commonwealth Trust. D.C. acknowledges support from St. John's College Cambridge and the Winton Programme (Cambridge) for the Physics of Sustainability.This is the final published version. It's also available at: http://pubs.acs.org/doi/abs/10.1021/jz501332v

Rewiring Chemical Networks Based on Dynamic Dithioacetal and Disulfide Bonds

The control of the connectivity between nodes of synthetic networks is still largely unexplored. To address this point we take advantage of a simple dynamic chemical system with two exchange levels that are mutually connected and can be activated simultaneously or sequentially. Dithioacetals and disulfides can be exchanged simultaneously under UV light in the presence of a sensitizer. Crossover reactions between both exchange processes produce a fully connected chemical network. On the other hand, the use of acid, base or UV light connects different nodes allowing network rewiring.Fil: Orrillo, Alfredo Gastón. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario; ArgentinaFil: la Venia, Agustina. 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: Escalante, Andrea Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario; ArgentinaFil: Furlan, Ricardo Luis Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario; Argentin