In Vitro and In Vivo Efficacy of Ether Lipid Edelfosine against Leishmania spp. and SbV-Resistant Parasites

Leishmaniasis represents a major international health problem, has a high morbidity and mortality rate, and is classified as an emerging and uncontrolled disease by the World Health Organization. The migration of population from endemic to nonendemic areas, and tourist activities in endemic regions are spreading the disease to new areas. Unfortunately, treatment of leishmaniasis is far from satisfactory, with only a few drugs available that show significant side-effects. Here, we show in vitro and in vivo evidence for the antileishmanial activity of the ether phospholipid edelfosine, being effective against a wide number of Leishmania spp. causing cutaneous, mucocutaneous and visceral leishmaniasis. Our experimental mouse and hamster models demonstrated not only a significant antileishmanial activity of edelfosine oral administration against different wild-type Leishmania spp., but also against parasites resistant to pentavalent antimonials, which constitute the first line of treatment worldwide. In addition, edelfosine exerted a higher antileishmanial activity and a lower proneness to generate drug resistance than miltefosine, the first drug against leishmaniasis that can be administered orally. These data, together with our previous findings, showing an anti-inflammatory action and a very low toxicity profile, suggest that edelfosine is a promising orally administered drug for leishmaniasis, thus warranting clinical evaluation

Thelaziosis in Humans, a Zoonotic Infection, Spain, 2011

After Thelazia callipaeda infection in dogs and cats were reported in Spain, a human case of thelaziosis in this country was reported, suggesting zoonotic transmission. The active reproductive status of this nematode in situ indicates that humans are competent hosts for this parasite

Nanometer-thick films of antimony oxide nanoparticles grafted on defective graphenes as heterogeneous base catalysts for coupling reactions

[EN] Films of few-layers defective N-doped or undoped graphene (10-15 nm) containing antimony oxide nanoparticles (15-30 nm) have been prepared on quartz by pyrolysis of alginate or chitosan adsorbing Sb(OAc)(3). XPS shows that the prevalent Sb oxidation state is +III, while thermoprogrammed CO2 desorption shows that these films exhibit basic sites. These thin films have used as basic catalysts to promote the Michael addition of active methylene compounds and the Henry condensation. These results have been rationalized by DFT calculations that have shown that undercoordinated or two-fold coordinated oxygen atoms on SbOx clusters can act as basic sites, providing a wide range of basic strength. (c) 2020 Elsevier Inc. All rights reserved.This work was supported by UEFISCDI (PN-III-P4-ID-PCE-2016-0146, nr. 121/2017 and project number PN-III-P1-1.1-TE-2016-2191, nr. 89/2018) and by the Spanish Ministry of Science and Innovation (Severo Ochoa and RTI2018-890237-CO2-1).Simion, A.; Candu, N.; Cojocaru, B.; Coman, SM.; Bucur, C.; Forneli Rubio, MA.; Primo Arnau, AM.... (2020). Nanometer-thick films of antimony oxide nanoparticles grafted on defective graphenes as heterogeneous base catalysts for coupling reactions. Journal of Catalysis. 390:135-149. https://doi.org/10.1016/j.jcat.2020.07.033S135149390Navalon, S., Dhakshinamoorthy, A., Alvaro, M., & Garcia, H. (2016). Metal nanoparticles supported on two-dimensional graphenes as heterogeneous catalysts. Coordination Chemistry Reviews, 312, 99-148. doi:10.1016/j.ccr.2015.12.005Blanita, G., & Lazar, M. D. (2013). Review of Graphene-Supported Metal Nanoparticles as New and Efficient Heterogeneous Catalysts. Micro and Nanosystems, 5(2), 138-146. doi:10.2174/1876402911305020009Zhu, Y., Murali, S., Cai, W., Li, X., Suk, J. W., Potts, J. R., & Ruoff, R. S. (2010). Graphene and Graphene Oxide: Synthesis, Properties, and Applications. Advanced Materials, 22(35), 3906-3924. doi:10.1002/adma.201001068Huang, C., Li, C., & Shi, G. (2012). Graphene based catalysts. Energy & Environmental Science, 5(10), 8848. doi:10.1039/c2ee22238hJoshi, R. K., Alwarappan, S., Yoshimura, M., Sahajwalla, V., & Nishina, Y. (2015). Graphene oxide: the new membrane material. Applied Materials Today, 1(1), 1-12. doi:10.1016/j.apmt.2015.06.002Miculescu, M., Thakur, V. K., Miculescu, F., & Voicu, S. I. (2016). Graphene-based polymer nanocomposite membranes: a review. Polymers for Advanced Technologies, 27(7), 844-859. doi:10.1002/pat.3751Trandafir, M.-M., Florea, M., Neaţu, F., Primo, A., Parvulescu, V. I., & García, H. (2016). Graphene from Alginate Pyrolysis as a Metal-Free Catalyst for Hydrogenation of Nitro Compounds. ChemSusChem, 9(13), 1565-1569. doi:10.1002/cssc.201600197Primo, A., Sánchez, E., Delgado, J. M., & García, H. (2014). High-yield production of N-doped graphitic platelets by aqueous exfoliation of pyrolyzed chitosan. Carbon, 68, 777-783. doi:10.1016/j.carbon.2013.11.068Hao, P., Zhao, Z., Leng, Y., Tian, J., Sang, Y., Boughton, R. I., … Yang, B. (2015). Graphene-based nitrogen self-doped hierarchical porous carbon aerogels derived from chitosan for high performance supercapacitors. Nano Energy, 15, 9-23. doi:10.1016/j.nanoen.2015.02.035Rizescu, C., Podolean, I., Albero, J., Parvulescu, V. I., Coman, S. M., Bucur, C., … Garcia, H. (2017). N-Doped graphene as a metal-free catalyst for glucose oxidation to succinic acid. Green Chemistry, 19(8), 1999-2005. doi:10.1039/c7gc00473gDhakshinamoorthy, A., Primo, A., Concepcion, P., Alvaro, M., & Garcia, H. (2013). Doped Graphene as a Metal-Free Carbocatalyst for the Selective Aerobic Oxidation of Benzylic Hydrocarbons, Cyclooctane and Styrene. Chemistry - A European Journal, 19(23), 7547-7554. doi:10.1002/chem.201300653Mateo, D., Esteve-Adell, I., Albero, J., Royo, J. F. S., Primo, A., & Garcia, H. (2016). 111 oriented gold nanoplatelets on multilayer graphene as visible light photocatalyst for overall water splitting. Nature Communications, 7(1). doi:10.1038/ncomms11819Latorre-Sánchez, M., Primo, A., & García, H. (2013). P-Doped Graphene Obtained by Pyrolysis of Modified Alginate as a Photocatalyst for Hydrogen Generation from Water-Methanol Mixtures. Angewandte Chemie International Edition, 52(45), 11813-11816. doi:10.1002/anie.201304505Primo, A., Esteve-Adell, I., Blandez, J. F., Dhakshinamoorthy, A., Álvaro, M., Candu, N., … García, H. (2015). High catalytic activity of oriented 2.0.0 copper(I) oxide grown on graphene film. Nature Communications, 6(1). doi:10.1038/ncomms9561Primo, A., Esteve-Adell, I., Coman, S. N., Candu, N., Parvulescu, V. I., & Garcia, H. (2015). One-Step Pyrolysis Preparation of 1.1.1 Oriented Gold Nanoplatelets Supported on Graphene and Six Orders of Magnitude Enhancement of the Resulting Catalytic Activity. Angewandte Chemie International Edition, 55(2), 607-612. doi:10.1002/anie.201508908Zhang, S., Yan, Z., Li, Y., Chen, Z., & Zeng, H. (2015). Atomically Thin Arsenene and Antimonene: Semimetal-Semiconductor and Indirect-Direct Band-Gap Transitions. Angewandte Chemie International Edition, 54(10), 3112-3115. doi:10.1002/anie.201411246Ji, J., Song, X., Liu, J., Yan, Z., Huo, C., Zhang, S., … Zeng, H. (2016). Two-dimensional antimonene single crystals grown by van der Waals epitaxy. Nature Communications, 7(1). doi:10.1038/ncomms13352Gibaja, C., Rodriguez-San-Miguel, D., Ares, P., Gómez-Herrero, J., Varela, M., Gillen, R., … Zamora, F. (2016). Few-Layer Antimonene by Liquid-Phase Exfoliation. Angewandte Chemie International Edition, 55(46), 14345-14349. doi:10.1002/anie.201605298Pumera, M., & Sofer, Z. (2017). 2D Monoelemental Arsenene, Antimonene, and Bismuthene: Beyond Black Phosphorus. Advanced Materials, 29(21), 1605299. doi:10.1002/adma.201605299Li, Q., Liu, M., Zhang, Y., & Liu, Z. (2015). Hexagonal Boron Nitride-Graphene Heterostructures: Synthesis and Interfacial Properties. Small, 12(1), 32-50. doi:10.1002/smll.201501766Tang, S., Wang, H., Zhang, Y., Li, A., Xie, H., Liu, X., … Jiang, M. (2013). Precisely aligned graphene grown on hexagonal boron nitride by catalyst free chemical vapor deposition. Scientific Reports, 3(1). doi:10.1038/srep02666Rendón-Patiño, A., Doménech, A., García, H., & Primo, A. (2019). A reliable procedure for the preparation of graphene-boron nitride superlattices as large area (cm × cm) films on arbitrary substrates or powders (gram scale) and unexpected electrocatalytic properties. Nanoscale, 11(6), 2981-2990. doi:10.1039/c8nr08377kElliott, B. ., Mackay, J. ., Clay, P., & Ashby, J. (1998). An assessment of the genetic toxicology of antimony trioxide. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 415(1-2), 109-117. doi:10.1016/s1383-5718(98)00065-5McCallum, R. I. (2005). Occupational exposure to antimony compounds. Journal of Environmental Monitoring, 7(12), 1245. doi:10.1039/b509118gGe, Y. Z., Han, C. H., & Zhang, D. (2011). Study of PET Depolymerization Catalyzed by Metal Oxide with Different Acidity/Basicity under Microwave Irradiation. Advanced Materials Research, 233-235, 1076-1079. doi:10.4028/www.scientific.net/amr.233-235.1076Gopiraman, M., Deng, D., Ganesh Babu, S., Hayashi, T., Karvembu, R., & Kim, I. S. (2015). Sustainable and Versatile CuO/GNS Nanocatalyst for Highly Efficient Base Free Coupling Reactions. ACS Sustainable Chemistry & Engineering, 3(10), 2478-2488. doi:10.1021/acssuschemeng.5b00542Cirujano, F. G., López-Maya, E., Rodríguez-Albelo, M., Barea, E., Navarro, J. A. R., & De Vos, D. E. (2017). Selective One-Pot Two-Step C−C Bond Formation using Metal-Organic Frameworks with Mild Basicity as Heterogeneous Catalysts. ChemCatChem, 9(21), 4019-4023. doi:10.1002/cctc.201700784Miguélez, J., Miyamura, H., & Kobayashi, S. (2017). A Polystyrene‐Supported Phase‐Transfer Catalyst for Asymmetric Michael Addition of Glycine‐Derived Imines to α,β‐Unsaturated Ketones. Advanced Synthesis & Catalysis, 359(17), 2897-2900. doi:10.1002/adsc.201700155Szőllősi, G., & Kozma, V. (2018). Design of Heterogeneous Organocatalyst for the Asymmetric Michael Addition of Aldehydes to Maleimides. ChemCatChem, 10(19), 4362-4368. doi:10.1002/cctc.201800919Szőllősi, G., Gombkötő, D., Mogyorós, A. Z., & Fülöp, F. (2018). Surface-Improved Asymmetric Michael Addition Catalyzed by Amino Acids Adsorbed on Laponite. Advanced Synthesis & Catalysis, 360(10), 1992-2004. doi:10.1002/adsc.201701627Zhang, J., Han, X., Wu, X., Liu, Y., & Cui, Y. (2019). Chiral DHIP- and Pyrrolidine-Based Covalent Organic Frameworks for Asymmetric Catalysis. ACS Sustainable Chemistry & Engineering, 7(5), 5065-5071. doi:10.1021/acssuschemeng.8b05887Xie, G., Zhang, J., & Ma, X. (2019). Compartmentalization of Multiple Catalysts into Outer and Inner Shells of Hollow Mesoporous Nanospheres for Heterogeneous Multi-Catalyzed/Multi-Component Asymmetric Organocascade. ACS Catalysis, 9(10), 9081-9086. doi:10.1021/acscatal.9b01608Tahir, N., Wang, G., Onyshchenko, I., De Geyter, N., Leus, K., Morent, R., & Van Der Voort, P. (2019). High-nitrogen containing covalent triazine frameworks as basic catalytic support for the Cu-catalyzed Henry reaction. Journal of Catalysis, 375, 242-248. doi:10.1016/j.jcat.2019.06.001Paul, A., Martins, L. M. D. R. S., Karmakar, A., Kuznetsov, M. L., Novikov, A. S., Guedes da Silva, M. F. C., & Pombeiro, A. J. L. (2020). Environmentally benign benzyl alcohol oxidation and C-C coupling catalysed by amide functionalized 3D Co(II) and Zn(II) metal organic frameworks. Journal of Catalysis, 385, 324-337. doi:10.1016/j.jcat.2020.03.035Zhou, T.-Y., Auer, B., Lee, S. J., & Telfer, S. G. (2019). Catalysts Confined in Programmed Framework Pores Enable New Transformations and Tune Reaction Efficiency and Selectivity. Journal of the American Chemical Society, 141(4), 1577-1582. doi:10.1021/jacs.8b11221Kannappan, L., & Rajmohan, R. (2020). Synthesis of structurally enhanced magnetite cored poly(propyleneimine) dendrimer nanohybrid material and evaluation of its functionality in sustainable catalysis of condensation reactions. Reactive and Functional Polymers, 152, 104579. doi:10.1016/j.reactfunctpolym.2020.104579Zabeti, M., Wan Daud, W. M. A., & Aroua, M. K. (2009). Activity of solid catalysts for biodiesel production: A review. Fuel Processing Technology, 90(6), 770-777. doi:10.1016/j.fuproc.2009.03.010Okuhara, T. (2002). Water-Tolerant Solid Acid Catalysts. Chemical Reviews, 102(10), 3641-3666. doi:10.1021/cr0103569Kiss, A. A., Dimian, A. C., & Rothenberg, G. (2006). Solid Acid Catalysts for Biodiesel Production –-Towards Sustainable Energy. Advanced Synthesis & Catalysis, 348(1-2), 75-81. doi:10.1002/adsc.200505160SONG, X., & SAYARI, A. (1996). Sulfated Zirconia-Based Strong Solid-Acid Catalysts: Recent Progress. Catalysis Reviews, 38(3), 329-412. doi:10.1080/01614949608006462Corma, A. (1997). Solid acid catalysts. Current Opinion in Solid State and Materials Science, 2(1), 63-75. doi:10.1016/s1359-0286(97)80107-6Johnson, O. (1955). Acidity and Polymerization Activity of Solid Acid Catalysts. The Journal of Physical Chemistry, 59(9), 827-831. doi:10.1021/j150531a007Weitkamp, J. (2000). Zeolites and catalysis. Solid State Ionics, 131(1-2), 175-188. doi:10.1016/s0167-2738(00)00632-9Tanabe, K. (1999). Industrial application of solid acid–base catalysts. Applied Catalysis A: General, 181(2), 399-434. doi:10.1016/s0926-860x(98)00397-4Hattori, H. (2001). Solid base catalysts: generation of basic sites and application to organic synthesis. Applied Catalysis A: General, 222(1-2), 247-259. doi:10.1016/s0926-860x(01)00839-0Ono, Y. (1997). Selective reactions over solid base catalysts. Catalysis Today, 38(3), 321-337. doi:10.1016/s0920-5861(97)81502-5Saugar, A. I., Márquez-Álvarez, C., Villar-Garcia, I. J., Welton, T., & Pérez-Pariente, J. (2016). Basicity and catalytic activity of porous materials based on a (Si,Al)-N framework. Applied Catalysis A: General, 520, 157-169. doi:10.1016/j.apcata.2016.04.012Ma, W., Zhang, X., Fan, J., Liu, Y., Tang, W., Xue, D., … Wang, C. (2019). Iron-Catalyzed Anti-Markovnikov Hydroamination and Hydroamidation of Allylic Alcohols. Journal of the American Chemical Society, 141(34), 13506-13515. doi:10.1021/jacs.9b05221Yang, S., Peng, L., Sun, D. T., Asgari, M., Oveisi, E., Trukhina, O., … Queen, W. L. (2019). A new post-synthetic polymerization strategy makes metal–organic frameworks more stable. Chemical Science, 10(17), 4542-4549. doi:10.1039/c9sc00135bDas, S., Goswami, A., Murali, N., & Asefa, T. (2013). Efficient Tertiary Amine/Weak Acid Bifunctional Mesoporous Silica Catalysts for Michael Addition Reactions. ChemCatChem, 5(4), 910-919. doi:10.1002/cctc.201200551Hammer, B., Hansen, L. B., & Nørskov, J. K. (1999). Improved adsorption energetics within density-functional theory using revised Perdew-Burke-Ernzerhof functionals. Physical Review B, 59(11), 7413-7421. doi:10.1103/physrevb.59.7413Latorre-Sánchez, M., Primo, A., Atienzar, P., Forneli, A., & García, H. (2014). p-n Heterojunction of Doped Graphene Films Obtained by Pyrolysis of Biomass Precursors. Small, 11(8), 970-975. doi:10.1002/smll.201402278Primo, A., Atienzar, P., Sanchez, E., Delgado, J. M., & García, H. (2012). From biomass wastes to large-area, high-quality, N-doped graphene: catalyst-free carbonization of chitosan coatings on arbitrary substrates. Chemical Communications, 48(74), 9254. doi:10.1039/c2cc34978gDhakshinamoorthy, A., Esteve Adell, I., Primo, A., & Garcia, H. (2017). Enhanced Activity of Ag Nanoplatelets on Few Layers of Graphene Film with Preferential Orientation for Dehydrogenative Silane–Alcohol Coupling. ACS Sustainable Chemistry & Engineering, 5(3), 2400-2406. doi:10.1021/acssuschemeng.6b02729Mateo, D., Esteve-Adell, I., Albero, J., Primo, A., & García, H. (2017). Oriented 2.0.0 Cu2O nanoplatelets supported on few-layers graphene as efficient visible light photocatalyst for overall water splitting. Applied Catalysis B: Environmental, 201, 582-590. doi:10.1016/j.apcatb.2016.08.033Simion, A., Candu, N., Coman, S. M., Primo, A., Esteve-Adell, I., Michelet, V., … Garcia, H. (2018). Bimetallic Oriented (Au /Cu2 O) vs. Monometallic 1.1.1 Au (0) or 2.0.0 Cu2 O Graphene-Supported Nanoplatelets as Very Efficient Catalysts for Michael and Henry Additions. European Journal of Organic Chemistry, 2018(44), 6185-6190. doi:10.1002/ejoc.201801443Wan Ngah, W. S., Teong, L. C., & Hanafiah, M. A. K. M. (2011). Adsorption of dyes and heavy metal ions by chitosan composites: A review. Carbohydrate Polymers, 83(4), 1446-1456. doi:10.1016/j.carbpol.2010.11.004Onsosyen, E., & Skaugrud, O. (2007). Metal recovery using chitosan. Journal of Chemical Technology & Biotechnology, 49(4), 395-404. doi:10.1002/jctb.280490410Puech, P., Plewa, J.-M., Mallet-Ladeira, P., & Monthioux, M. (2016). Spatial confinement model applied to phonons in disordered graphene-based carbons. Carbon, 105, 275-281. doi:10.1016/j.carbon.2016.04.048Dervishi, E., Ji, Z., Htoon, H., Sykora, M., & Doorn, S. K. (2019). Raman spectroscopy of bottom-up synthesized graphene quantum dots: size and structure dependence. Nanoscale, 11(35), 16571-16581. doi:10.1039/c9nr05345jTamor, M. A., & Vassell, W. C. (1994). Raman ‘‘fingerprinting’’ of amorphous carbon films. Journal of Applied Physics, 76(6), 3823-3830. doi:10.1063/1.357385Zhang, H., Sun, K., Feng, Z., Ying, P., & Li, C. (2006). Studies on the SbOx species of SbOx/SiO2 catalysts for methane-selective oxidation to formaldehyde. Applied Catalysis A: General, 305(1), 110-119. doi:10.1016/j.apcata.2006.02.038Wan, F., Guo, J.-Z., Zhang, X.-H., Zhang, J.-P., Sun, H.-Z., Yan, Q., … Wu, X.-L. (2016). In Situ Binding Sb Nanospheres on Graphene via Oxygen Bonds as Superior Anode for Ultrafast Sodium-Ion Batteries. ACS Applied Materials & Interfaces, 8(12), 7790-7799. doi:10.1021/acsami.5b12242Primo, A., Franconetti, A., Magureanu, M., Mandache, N. B., Bucur, C., Rizescu, C., … Garcia, H. (2018). Engineering active sites on reduced graphene oxide by hydrogen plasma irradiation: mimicking bifunctional metal/supported catalysts in hydrogenation reactions. Green Chemistry, 20(11), 2611-2623. doi:10.1039/c7gc03397dWei, D., Liu, Y., Wang, Y., Zhang, H., Huang, L., & Yu, G. (2009). Synthesis of N-Doped Graphene by Chemical Vapor Deposition and Its Electrical Properties. Nano Letters, 9(5), 1752-1758. doi:10.1021/nl803279tCincotto, F. H., Canevari, T. C., Machado, S. A. S., Sánchez, A., Barrio, M. A. R., Villalonga, R., & Pingarrón, J. M. (2015). Reduced graphene oxide-Sb2O5 hybrid nanomaterial for the design of a laccase-based amperometric biosensor for estriol. Electrochimica Acta, 174, 332-339. doi:10.1016/j.electacta.2015.06.013Kumar, C. R., Anand, N., Kloekhorst, A., Cannilla, C., Bonura, G., Frusteri, F., … Heeres, H. J. (2015). Solvent free depolymerization of Kraft lignin to alkyl-phenolics using supported NiMo and CoMo catalysts. Green Chemistry, 17(11), 4921-4930. doi:10.1039/c5gc01641jJosé Velasco, M., Rubio, F., Rubio, J., & Oteo, J. L. (1999). DSC and FT-IR analysis of the drying process of titanium alkoxide derived precipitates. Thermochimica Acta, 326(1-2), 91-97. doi:10.1016/s0040-6031(98)00580-2Kaiser, B., Bernhardt, T. M., Kinne, M., Rademann, K., & Heidenreich, A. (1999). Formation, stability, and structures of antimony oxide cluster ions. The Journal of Chemical Physics, 110(3), 1437-1449. doi:10.1063/1.478019Aljama, H., Nørskov, J. K., & Abild-Pedersen, F. (2017). Theoretical Insights into Methane C–H Bond Activation on Alkaline Metal Oxides. The Journal of Physical Chemistry C, 121(30), 16440-16446. doi:10.1021/acs.jpcc.7b05838Latimer, A. A., Aljama, H., Kakekhani, A., Yoo, J. S., Kulkarni, A., Tsai, C., … Nørskov, J. K. (2017). Mechanistic insights into heterogeneous methane activation. Physical Chemistry Chemical Physics, 19(5), 3575-3581. doi:10.1039/c6cp08003