Receptor assay-guided isolation of anti-GABAergic insecticidal alkaloids from a fungal culture.
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.
Kuriyama
Tadahiko
T
Department of Life Science and Biotechnology, Faculty of Life and Environmental Science, Shimane University, Matsue, Shimane 690-8504, Japan.
Kakemoto
Eiji
E
Takahashi
Nobutoshi
N
Imamura
Kei-ichi
K
Oyama
Kazuhiko
K
Suzuki
Emiko
E
Harimaya
Kenzo
K
Yaguchi
Takashi
T
Ozoe
Yoshihisa
Y
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
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