CONTROL OF OVINE TRICOSTRONGILIDOSIS: DESIGN, SYNTHESIS AND CLINICAL TRIALS OF EFFECTIVENESS OF NEW ACTION MOLECULES ANTIHELMINTICA (Q3189471): Difference between revisions
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(Created claim: summary (P836): GASTROINTESTINAL TRICOSTRONGILIDES CAUSE DIRECT AND INDIRECT LOSSES OF GREAT ECONOMIC IMPACT DUE TO REDUCED PRODUCTIVE YIELDS AND INCREASED HEALTH COSTS IN SHEEP. CURRENT THERAPEUTIC TREATMENTS ARE LEADING TO THE EMERGENCE OF RESISTANCE TO CHOICE PHARMACOS, WHICH POSES A SERIOUS PROBLEM FOR THE CONTROL OF PARASITIC GASTROENTERITIS, INCREASING PRODUCTION COSTS AND REDUCING THE EFFICIENCY OF THE SYSTEM AND THE QUALITY OF THE PRODUCTS. THEREFORE, I...) |
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CONTROL OF OVINE TRICOSTRONGILIDOSIS: DESIGN, SYNTHESIS AND CLINICAL TRIALS OF EFFECTIVENESS OF NEW ACTION MOLECULES ANTIHELMINTICA | |||
Revision as of 21:11, 12 October 2021
Project Q3189471 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | CONTROL OF OVINE TRICOSTRONGILIDOSIS: DESIGN, SYNTHESIS AND CLINICAL TRIALS OF EFFECTIVENESS OF NEW ACTION MOLECULES ANTIHELMINTICA |
Project Q3189471 in Spain |
Statements
60,500.0 Euro
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121,000.0 Euro
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50.0 percent
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30 December 2016
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31 December 2020
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UNIVERSIDAD DE LEON
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42°38'2.94"N, 5°58'17.11"W
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24089
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LOS TRICOSTRONGILIDOS GASTROINTESTINALES CAUSAN PERDIDAS DIRECTAS E INDIRECTAS DE GRAN REPERCUSION ECONOMICA POR LA DISMINUCION DE LOS RENDIMIENTOS PRODUCTIVOS Y AUMENTO DE LOS COSTES SANITARIOS EN EL GANADO OVINO. LOS TRATAMIENTOS TERAPEUTICOS ACTUALES ESTAN DANDO LUGAR A LA APARICION DE RESISTENCIAS A LOS FARMACOS DE ELECCION, LO QUE SUPONE UN GRAVE PROBLEMA PARA EL CONTROL DE LAS GASTROENTERITIS PARASITARIAS, INCREMENTANDO LOS COSTES DE PRODUCCION Y REDUCIENDO LA EFICACIA DEL SISTEMA Y LA CALIDAD DE LOS PRODUCTOS. POR LO TANTO, EN EL PRESENTE PROYECTO PROPONEMOS UNA ESTRATEGIA ¿FROM HIT TO LEAD TO DRUG CANDIDATE¿ BASADA EN EL CRIBADO INICIAL DE VARIOS LIGNANOS Y OTRAS SERIES DE COMPUESTOS, CON ACTIVIDAD ANTIMITOTICA Y ANTIPARASITARIA PROBADA EN OTROS ORGANISMOS, UTILIZANDO PARA ELLO LOS ENSAYOS IN VITRO DE ECLOSION DE HUEVOS (EHA) Y DE LA INHIBICION DE LA INGESTION LARVARIA (LFIA), ASI COMO TAMBIEN SE COMPROBARA LA CAPACIDAD DE INHIBICION DE LA POLIMERIZACION DE LA TUBULINA RECOMBINANTE DEL NEMATODO TELADORSAGIA CIRCUMCINCTA (TANTO DE CEPAS SUSCEPTIBLES COMO DE RESISTENTES). PARA ELLO TOMAREMOS DE PARTIDA UNA SERIE DE MOLECULAS EN LAS QUE PREVIAMENTE YA SE HA DEMOSTRADO SU CAPACIDAD OVICIDA Y LARVICIDA EN ENSAYOS IN VITRO REALIZADOS EN UN PROYECTO ANTERIOR. _x000D_ LAS MOLECULAS QUE PRESENTEN ACTIVIDAD ANTIHELMINTICA LEVE O MODERADA, INCLUYENDO INICIALMENTE ALGUNAS PRELIMINARES DEL PROYECTO PREVIO, SE SOMETERAN A PROCESOS DE OPTIMIZACION ESTRUCTURAL MEDIANTE MODELADO Y CALCULO MOLECULAR PARA MEJORAR SU ACTIVIDAD ANTITUBULINA. TRAS LAS MODIFICACIONES ESTRUCTURALES SE VOLVERAN A REALIZAR LOS BIOENSAYOS PERTINENTES Y, CON AQUELLAS QUE PRESENTEN LA ACTIVIDAD MAS POTENTE SE REALIZARAN LOS ENSAYOS DE TOXICIDAD PERTINENTES ASI COMO LA PREDICCION DE SUS PROPIEDADES FISICOQUIMICAS. AQUEL COMPUESTOS CON MAYOR EFECTO IN VITRO FRENTE A LOS NEMATODOS, Y QUE DEMUESTREN UNA BAJA TOXICIDAD, SE EVALUARA EN UNA INFECCION EXPERIMENTAL OVINA, PARA ESTABLECER SU EFICACIA ANTIHELMINTICA Y SU SEGURIDAD. EN CASO DE NO ENCONTRAR NINGUNA MOLECULA CON ACTIVIDAD SATISFACTORIA Y BAJA TOXICIDAD PARA EL ENSAYO IN VIVO, HAREMOS UNA SELECCION DE MOLECULAS, CON MAYOR ACTIVIDAD Y MENOR TOXICIDAD, PARA SER PROBADAS EN COMBINACION CON EL FARMACO ALBENDAZOL EN LOS ENSAYOS IN VITRO Y UTILIZANDO UNA CEPA RESISTENTE. LA COMBINACION MAS EFECTIVA SE PROBARA EN CORDEROS INFECTADOS EXPERIMENTALMENTE CON LA MISMA CEPA RESISTENTE. (Spanish)
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GASTROINTESTINAL TRICOSTRONGILIDES CAUSE DIRECT AND INDIRECT LOSSES OF GREAT ECONOMIC IMPACT DUE TO REDUCED PRODUCTIVE YIELDS AND INCREASED HEALTH COSTS IN SHEEP. CURRENT THERAPEUTIC TREATMENTS ARE LEADING TO THE EMERGENCE OF RESISTANCE TO CHOICE PHARMACOS, WHICH POSES A SERIOUS PROBLEM FOR THE CONTROL OF PARASITIC GASTROENTERITIS, INCREASING PRODUCTION COSTS AND REDUCING THE EFFICIENCY OF THE SYSTEM AND THE QUALITY OF THE PRODUCTS. THEREFORE, IN THIS PROJECT WE PROPOSE A STRATEGY FROM HIT TO LEAD TO DRUG CANDIDATE, BASED ON THE INITIAL SCREENING OF SEVERAL LIGNANS AND OTHER SERIES OF COMPOUNDS, WITH ANTIMITOTICA AND ANTIPARASITIC ACTIVITY TESTED IN OTHER ORGANISMS, USING IN VITRO EGG HATCHING (EHA) AND LARVAL INGESTION INHIBITION (LFIA) TESTS, AS WELL AS THE ABILITY TO INHIBIT THE POLYMERISATION OF RECOMBINANT TUBULIN NEMATODE TELADORSAGIA CIRCUMCINCTA (BOTH SUSCEPTIBLE AND RESISTANT STRAINS). TO THIS END, WE WILL START A SERIES OF MOLECULES IN WHICH THEIR OVICIDAL AND LARVICIDE CAPACITY HAS PREVIOUSLY BEEN DEMONSTRATED IN IN VITRO ASSAYS CARRIED OUT IN A PREVIOUS PROJECT. _x000D_ the molecules that present ANTIHELMINTICA LEVE or MODERATE ACTIVITY, INCLUDING INNICIALLY THE PRIVACIAL PROJECT PROJECT PROJECT, BE submitted to procedures of STRUCTURAL MEDITURAL MODELATED OPTIMISATION AND MOLECULAR QALCULE to improve their antitubulin activity. FOLLOWING THE STRUCTURAL MODIFICATIONS, THE RELEVANT BIOASSAYS WILL BE RE-PERFORMED AND THE RELEVANT TOXICITY TESTS AND THE PREDICTION OF THEIR PHYSICOCHEMICAL PROPERTIES WILL BE PERFORMED WITH THOSE WITH THE MOST POTENT ACTIVITY. THOSE COMPOUNDS WITH THE GREATEST EFFECT IN VITRO AGAINST NEMATODES, AND SHOWING LOW TOXICITY, WERE EVALUATED IN AN EXPERIMENTAL OVINE INFECTION TO ESTABLISH THEIR EFFICACY AND SAFETY. IF NO MOLECULATE IS FOUND WITH SATISFACTORY ACTIVITY AND LOW TOXICITY FOR THE IN VIVO ASSAY, WE WILL SELECT MOLECULES, WITH HIGHER ACTIVITY AND LESS TOXICITY, TO BE TESTED IN COMBINATION WITH THE PHARMACO ALBENDAZOLE IN IN VITRO ASSAYS AND USING A RESISTANT STRAIN. THE MOST EFFECTIVE COMBINATION WILL BE TESTED ON EXPERIMENTALLY INFECTED LAMBS WITH THE SAME RESISTANT STRAIN. (English)
12 October 2021
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León
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Identifiers
AGL2016-79813-C2-1-R
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