Receptor Assay-Guided Isolation of Anti-GABAergic Insecticidal Alkaloids from a Fungal Culture

摘要

The gamma-aminobutyric acid (GABA) receptor bears sites of action for insecticides.To discover GABA receptor-directed insecticides in natural products,fungal culture extracts were screened for their ability to inhibit specific binding of the radiolabeled noncompetitive antagonist [3H]1-(4-ethynylphenyl)-4-n-propyl-2,6,7-trioxabicyclo[2.2.2]octane to housefly head membranes.The screening efforts led to the isolation of two alkaloids from Aspergillus terreus:PF1198A (alantrypinone) and PF1198B (seran-trypinone),which had IC_(50) values of 0.34 and 2.1muM,respectively,in this assay.These compounds were ca.47-61-fold selective for housefly vs rat GABA receptors.Both compounds showed insecticidal activity against Myzus persicae in the range of 100-500 ppm.Binding assay-guided screening should provide significant opportunities for the identification of novel and selective insecticides.