A5082998016- Research on Leishmaniasis Studies
- Trypanosoma species research and implications
- Cancer therapeutics and mechanisms
- Synthesis and Biological Evaluation
- Polyamine Metabolism and Applications
- Parasites and Host Interactions
- Bioactive Compounds and Antitumor Agents
- Toxin Mechanisms and Immunotoxins
- Synthesis and Biological Activity
- Biochemical and Molecular Research
- Mosquito-borne diseases and control
- Phenothiazines and Benzothiazines Synthesis and Activities
- Chronic Myeloid Leukemia Treatments
- Insect and Pesticide Research
GlaxoSmithKline (Spain)
2021
Universidad de León
2011-2019
Universidad de León
2011-2019
Centro de Biología Molecular Severo Ochoa
2019
Universidad Autónoma de Madrid
2019
Consejo Superior de Investigaciones Científicas
2019
Background Visceral leishmaniasis (VL) is hypoendemic in the Mediterranean region, where it caused by protozoan Leishmania infantum. An effective vaccine for humans not yet available and severe side-effects of drugs clinical use, linked to parenteral administration route most them, are significant concerns current leishmanicidal medicines. New desperately needed treat VL phenotype-based High Throughput Screenings (HTS) appear be suitable achieve this goal coming years. Methodology/Principal...
Background Leishmania major cutaneous leishmaniasis is an infectious zoonotic disease. It produced by a digenetic parasite, which resides in the phagolysosomal compartment of different mammalian macrophage populations. There urgent need to develop new therapies (drugs) against this neglected disease that hits developing countries. The main goal work establish easier and cheaper tool choice for real-time monitoring establishment progression pathology either BALB/c mice or vitro assays. To...
Visceral leishmaniasis is an emerging neglected tropical disease (NTD) caused by the protozoan Leishmania infantum in countries bordering Mediterranean Basin. Currently there no effective vaccine against this disease, and therapeutic approach based on toxic derivatives of Sb(V). Therefore, discovery new targets development drugs designed to inhibit them comprise extremely important fighting disease. DNA topoisomerases (Top) have been identified as promising for therapy leishmaniasis. These...
Drug discovery programs sponsored by public or private initiatives pursue the same ambitious goal: a crushing defeat of major Neglected Tropical Diseases (NTDs) during this decade. Both target-based and target-free screenings have pros cons when it comes to finding potential small-molecule leads among chemical libraries consisting myriads compounds. Within strategy, crystals pathogen recombinant-proteins are being used obtain three-dimensional (3D) structures in silico for structure-based...
Background The mode of reproduction in Leishmania spp has been argued to be essentially clonal. However, recent data (genetic analysis populations and co-infections sand flies) have proposed the existence a non-obligate sexual cycle extracellular stage parasite within fly vector. In this article we propose intraclonal genetic exchange natural vector infantum. Methodology/Principal findings We developed transgenic L. infantum lines expressing drug resistance markers linked green red...
Abstract The novel fatty acids (2 R ,5 Z ,9 )‐2‐methoxy‐25‐methyl‐5,9‐hexacosadienoic acid ( 1a ) and )‐2‐methoxy‐24‐methyl‐5,9‐hexacosadienoic 1b were isolated in 80 % purity from the Caribbean sponge Asteropus niger by chloroform/methanol extraction followed solvent partitioning silica gel column chromatography. compounds characterized utilizing a combination of gas chromatography‐mass spectrometry, nuclear magnetic resonance, circular dichroism. Acids not detected phospholipids (PtdCho...
Background Visceral leishmaniasis is a neglected parasitic disease with no vaccine available and its pharmacological treatment reduced to limited number of unsafe drugs. The scarce readiness new antileishmanial drugs even more alarming when relapses appear or the occurrence hard-to-treat resistant strains detected. In addition, there gap between initial late stages drug development, which greatly delays selection leads for subsequent studies. Methodology/Principal findings order address...
Sponges biosynthesize α-methoxylated fatty acids with unusual biophysical and biological properties in some cases they display enhanced anticancer activities. However, the antiprotozoal of have been less studied. In this work, we describe total synthesis (5Z,9Z)-(±)-2-methoxy-5, 9-eicosadienoic acid (1) its acetylenic analog (±)-2-methoxy-5,9-eicosadiynoic (2), report that inhibit (EC₅₀ values between 31 22 µM) Leishmania donovani DNA topoisomerase IB enzyme (LdTopIB). The inhibition LdTopIB...
Leishmania donovani, the causative organism for visceral leishmaniasis, contains a unique heterodimeric DNA-topoisomerase IB (LdTopIB). LdTopIB is heterodimer made up of large subunit and small that must interact with each other to build an active enzyme able solve topological tensions on DNA. As located within nucleus, one or more nuclear localization signals (NLS) should exist ensure its translocation. In this report three novel NLS have been identified through sequential deletion study...
Methionine adenosyltransferase (MAT) is an important enzyme for metabolic processes, to the extent that its product, S-adenosylmethionine (AdoMet), plays a key role in trans-methylation, trans-sulphuration and polyamine synthesis. Previous studies have shown MAT-overexpressing strain of Leishmania donovani controls AdoMet production, keeping intracellular concentration at levels are compatible with cell survival. This unexpected result, together fact MAT activity abundance changed time...
DNA topoisomerases are considered consolidated druggable targets against diseases produced by trypanosomatids. Several reports indicated that indenoisoquinolines, a family of non-camptothecinic based topoisomerase poisons, have strong leishmanicidal effect both in vitro and vivo murine models visceral leishmaniasis. The antileishmanial the indenoisoquinolines implies several mechanisms include stabilization cleavage complex, histone H2A phosphorylation fragmentation. A series 20 compounds...
Chagas disease (CD) is a human caused by Trypanosoma cruzi . Whilst endemic in Latin America, the spread around world due to migration flows, being estimated that 8 million people are infected worldwide and over 10,000 die yearly of complications linked CD. Current chemotherapeutics restricted only two drugs, i.e. benznidazole (BNZ) nifurtimox (NIF), both nitroaromatic compounds sharing mechanism action exerting suboptimal efficacy serious adverse effects. Recent clinical trials conducted...
Abstract Background Canine leishmaniasis is a zoonotic disease caused by Leishmania infantum , being the dogs one of major reservoirs human visceral leishmaniasis. DNA topology consolidated target for drug discovery. In this regard, topoisomerase IB – enzymes controlling has been poisoned hundreds compounds that increase fragility and cell death. Aromathecins are novel molecules with multiheterocyclic ring scaffold have higher stability than camptothecins. Results showed strong activity...