A5074540400- Research on Leishmaniasis Studies
- Trypanosoma species research and implications
- Insect Pest Control Strategies
- Vector-borne infectious diseases
- Insect and Pesticide Research
- Leptospirosis research and findings
- Synthesis and biological activity
- X-ray Diffraction in Crystallography
- Chemical Synthesis and Analysis
- Biochemical and Molecular Research
- Crystallization and Solubility Studies
- Mosquito-borne diseases and control
- Synthesis and Biological Evaluation
- Coenzyme Q10 studies and effects
- Insect behavior and control techniques
- HIV Research and Treatment
- Insect-Plant Interactions and Control
- Protein Structure and Dynamics
- Dermatological diseases and infestations
- Marine Ecology and Invasive Species
- Enzyme function and inhibition
- Identification and Quantification in Food
- Malaria Research and Control
- RNA and protein synthesis mechanisms
- Bartonella species infections research
Universidad de Granada
2015-2024
University of Dundee
2018-2024
Wellcome Centre for Anti-Infectives Research
2018-2023
Wellcome Trust
2018
Visceral leishmaniasis (VL), caused by the protozoan parasites Leishmania donovani and L. infantum, is responsible for ∼30 000 deaths annually. Available treatments are inadequate, there a pressing need new therapeutics. N-Myristoyltransferase (NMT) remains one of few genetically validated drug targets in these parasites. Here, we sought to pharmacologically validate this enzyme Leishmania. A focused set 1600 pyrazolyl sulfonamide compounds was screened against major NMT robust...
Visceral leishmaniasis (VL) is a parasitic disease endemic across multiple regions of the world and fatal if untreated. Current therapies are unsuitable, there an urgent need for safe, short-course, low-cost oral treatments to combat this neglected disease. The benzoxaborole chemotype has previously delivered clinical candidates treatment other diseases. Here, we describe development optimization series, leading identification compounds with potent in vitro vivo antileishmanial activity....
Abstract Identifying how small molecules act to kill malaria parasites can lead new “chemically validated” targets. By pressuring Plasmodium falciparum asexual blood stage with three novel structurally-unrelated antimalarial compounds (MMV665924, MMV019719 and MMV897615), performing whole-genome sequence analysis on resistant parasite lines, we identify multiple mutations in the P. acyl-CoA synthetase (ACS) genes Pf ACS10 (PF3D7_0525100, M300I, A268D/V, F427L) ACS11 (PF3D7_1238800, F387V,...
The aim of the present study was to assess in vitro and vivo activity (−)-α-bisabolol (1) against etiological agents visceral leishmaniasis. Bone-marrow-derived macrophages were infected with Leishmania infantum or L. donovani promastigotes incubated at different concentrations. Pentamidine isethionate meglumine antimoniate used as reference drugs. Inhibitory concentration 50% (IC50) cytotoxic (CC50) calculated. Balb/c mice intraperitoneally stationary-phase promastigotes. They treated doses...
There is a pressing need for new medicines to prevent and treat malaria. Most antimalarial drug discovery reliant upon phenotypic screening. However, with the development of improved target validation strategies, target-focused approaches are now being utilized. Here, we describe toolkit support therapeutic exploitation promising target, lysyl tRNA synthetase (PfKRS). The includes resistant mutants probe resistance mechanisms on-target engagement specific chemotypes; hybrid KRS protein...
There is limited information regarding the role of wild mammals in transmission dynamics Leishmania infantum. A potential human leishmaniasis hot spot was detected southern Spain that could not be explained solely by canine prevalence. The aim this work to analyse involvement rabbits as main factor affecting Mediterranean spot. survey rabbits, dogs and sand flies conducted cases environment. nearby region without clinical used reference control. 51 shot hunters were analysed molecular...
Visceral leishmaniasis (VL) caused by the protozoan parasite Leishmania infantum, is one of most important zoonotic diseases affecting dogs and humans in Mediterranean area. The presence infected as main reservoir host L. infantum regarded significant risk for potential human infection. We have studied susceptibility profile to antimony other anti-leishmania drugs (amphotericin B, miltefosine, paromomycin) isolates extracted from a dog before after two therapeutic interventions with...
The aim of this study was to explore Leishmania infantum epidemiology through a One Health approach that promotes better estimation leishmaniasis burden and deeper understanding the spatial distribution key actors parasite life cycle (vectors, reservoirs humans). We conducted 14-year mixed retrospective prospective cases in an endemic area southern Spain (Granada province), estimate human incidence its association with vector presence, cryptic rates canine prevalence. found annual linear...
Phenotypic screening identified a benzothiophene compound with activity against Leishmania donovani, the causative agent of visceral leishmaniasis. Using multiple orthogonal approaches, oxidosqualene cyclase (OSC), key enzyme sterol biosynthesis, was as target this racemic and its enantiomers. Whole genome sequencing genome-wide overexpression library confirmed that OSC gene amplification is associated resistance to 1. Introduction an ectopic copy into wild-type cells reduced susceptibility...
Leishmaniasis is a neglected tropical disease; there currently no vaccine and treatment reliant upon handful of drugs suffering from multiple issues including toxicity resistance. There critical need for development new fit-for-purpose therapeutics, with reduced targeting mechanisms to overcome One enzyme meriting investigation as potential drug target in Leishmania M17 leucyl-aminopeptidase (LAP). Here, we aimed chemically validate LAP L. major through identification potent selective...
Cutaneous leishmaniasis (CL) caused by Leishmania tropica is emerging in new areas, initially as outbreaks and then establishing endemic foci. There little evidence of the risk factors effectiveness existing control measures, what limits our ability to generalize different epidemiological settings. The disease described anthroponotic; however, zoonotic have been reported some countries. Our aim was identify a recently focus Morocco order design more effective programmes. A case–control study...
There is currently no reliable treatment for the management of cutaneous leishmaniasis, and intralesional antimonial injections remain main treatment. The present work aims at evaluating antileishmanial effectiveness safety (-)-α-bisabolol (1) in a novel topical formulation on leishmaniasis model involving Leishmania tropica-infected Syrian hamsters. with 1 reduced lesion thickness to 56% 2.5%, showing higher efficacy than reference control, meglumine antimoniate. Other regimens (ointment 1%...
Phenotypic screening identified an arylsulfonamide compound with activity against Trypanosoma cruzi , the causative agent of Chagas’ disease. Comprehensive mode action studies revealed that this primarily targets T. proteasome, binding at interface between β4 and β5 subunits catalyze chymotrypsin-like activity.
Cutaneous leishmaniasis (CL) is underestimated in Spain as other European countries due to the polymorphism of its clinical manifestations and histopathological features discouraging doctors from suspecting leishmaniasis. Mucosal (ML) are misdiagnosed fact that they often mimic cancer.Given may be masked different granulomatous diseases Leishmania infantum endemic areas, aim this study was verify misdiagnosing contributes improvement CL/ML diagnosis.A retrospective involving formalin-fixed...
Abstract Objectives The introduction of leishmaniasis in a new area requires well‐established population the sandfly vector species parasite. No autochthonous cases anthroponotic cutaneous have been detected southwestern Europe, and Leishmania infantum is only causative agent this area. Phlebotomus sergenti, main tropica, commonly found Iberian Peninsula at sufficient densities to be able act as vector. It characterised by high genetic diversity classified four mitochondrial lineages. Our...
Leishmania (L.) infantum causes visceral, cutaneous, and mucosal leishmaniasis in humans canine dogs. Herein, we describe that O-alkyl hydroxamate derivatives displayed potent selective vitro activity against the amastigote stage of L. while no was observed promastigotes. Compound 5 showed vivo infantum. Moreover, combination compound supported on gold nanoparticles meglumine antimoniate also effective improved these compounds compared to individual treatment. Docking studies did not reach...