ABSTRACT
Widdrol (1) was tested against the necrotrophic plant pathogens Botrytis cinerea and Colletotrichum gloeosporioides. While 1 was found to be inactive against C. gloeosporioides, it showed a selective and effective control of B. cinerea, significantly inhibiting the mycelial growth of the fungus at concentrations of 100 ppm and above. In addition, the biotransformation of 1 by both fungi was studied. Incubation with C. gloeosporioides and B. cinerea afforded four and one biotransformation products (2-6), respectively. Biotransformation with C. gloeosporioides was highly regioselective, yielding for the most part oxidation products at C-10: 10-oxowiddrol (2), 10beta-hydroxywiddrol (3), 10alpha-hydroxywiddrol (4), and 14alpha-hydroxywiddrol (5). The structures of all products were determined on the basis of their spectroscopic data, including coupling constants, two-dimensional NMR analysis (heteronuclear multiple quantum coherence, heteronuclear multiple bond correlation, and nuclear Overhauser enhancement spectroscopy), and nuclear Overhauser effect. The biotransformation products were then tested against B. cinerea and found to be inactive. These results shed further light on the structural modifications, which may be necessary to develop selective fungal control agents against B. cinerea.
Subject(s)
Benzocycloheptenes/metabolism , Benzocycloheptenes/pharmacology , Botrytis/drug effects , Colletotrichum/drug effects , Fungicides, Industrial/pharmacology , Botrytis/metabolism , Colletotrichum/metabolism , Fungicides, Industrial/metabolism , Magnetic Resonance SpectroscopyABSTRACT
El descubrimiento de Cromoglicato Disódico representa un importante progreso en el tratamiento del asma. Sin embargo, debido a su pobre solubilidad e incapacidad para ser absorbido del tracto gastrointestinal, la forma galénica de este medicamento es una de sus mayores desventajas relativas en la práctica clínica. Esto ha estimulado los estudios para encontrar agentes terapéuticos que sean activos y bien tolerados por vía oral. Un agente es el Ketotifeno (HC-20-511), el cual está químicamente relacionado al grupo de sustancias del tipo cicloheptathiopheno. Este producto ha mostrado varias propiedades farmacológicas en enfermedades alérgicas. Ha demostrado muy bajo nivel de toxicidad y una rápida y completa absorción a través del tubo digestivo. Nosotros reportamos la eficacia clínica y la tolerancia del Ketotifeno en un grupo de pacientes con asma bronquial de leve a moderada. El análisis estadístico de la información muestra que el uso del Ketotifeno ayuda a controlar los síntomas del asma y es una droga prometedora en el tratamiento profiláctico del asma