title: Receptor assay-guided isolation of anti-GABAergic insecticidal alkaloids from a fungal culture.
abstract: 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 (serantrypinone), which had IC50 values of 0.34 and 2.1 microM, 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.
authors.affiliation: Department of Life Science and Biotechnology, Faculty of Life and Environmental Science, Shimane University, Matsue, Shimane 690-8504, Japan.
authors.forename: Tadahiko
authors.initials: T
authors.lastname: Kuriyama
authors.forename: Eiji
authors.initials: E
authors.lastname: Kakemoto
authors.forename: Nobutoshi
authors.initials: N
authors.lastname: Takahashi
authors.forename: Kei-ichi
authors.initials: K
authors.lastname: Imamura
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Oyama
authors.forename: Emiko
authors.initials: E
authors.lastname: Suzuki
authors.forename: Kenzo
authors.initials: K
authors.lastname: Harimaya
authors.forename: Takashi
authors.initials: T
authors.lastname: Yaguchi
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Ozoe
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification; D000818:Animals; D001230:Aspergillus / Q000378:metabolism; D001923:Brain Chemistry; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000037:antagonists & inhibitors / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry; D018756:GABA Antagonists / Q000737:chemistry / Q000302:isolation & purification; D006793:Houseflies; D007211:Indoles / Q000737:chemistry / Q000302:isolation & purification; D007306:Insecticides / Q000302:isolation & purification*; D011799:Quinazolines / Q000737:chemistry / Q000302:isolation & purification; D051381:Rats; D018079:Receptors, GABA / Q000378:metabolism*; D014316:Tritium
chemical_list: D000470:Alkaloids; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018756:GABA Antagonists; D007211:Indoles; D007306:Insecticides; D011799:Quinazolines; D018079:Receptors, GABA; C115545:alantrypinone; C446564:serantrypinone; D014316:Tritium; C091518:1-(4-ethynylphenyl)-4-propyl-2,6,7-trioxabicyclo(2.2.2)octane