RESUMO
A novel class of synthetic tubulin polymerization disruptors, based on a substituted pyrazin-2-one core, has been discovered. These molecules have proven to be potent broad spectrum fungicides, with activity on agriculturally important ascomycete and basidiomycete pathogens. They have also been found to be particularly potent against human rhabdomyosarcoma cells. Using an efficient synthetic route, the agricultural and medicinal activity was explored.
Assuntos
Antineoplásicos/farmacologia , Fungicidas Industriais/farmacologia , Pirazinas/farmacologia , Moduladores de Tubulina/química , Moduladores de Tubulina/farmacologia , Tubulina (Proteína)/metabolismo , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Fungicidas Industriais/química , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Pirazinas/química , Relação Estrutura-AtividadeRESUMO
Oxathiapiprolin is the first member of a new class of piperidinyl thiazole isoxazoline fungicides with exceptional activity against plant diseases caused by oomycete pathogens. It acts via inhibition of a novel fungal target-an oxysterol binding protein-resulting in excellent preventative, curative and residual efficacy against key diseases of grapes, potatoes and vegetables. Oxathiapiprolin is being developed globally as DuPont™ Zorvec™ disease control with first registration and sales anticipated in 2015. The discovery, synthesis, optimization and biological efficacy are presented.
