Modulation of Anopheles gambiae Epsilon glutathione transferase activity by plant natural products in vitro.
Elevated glutathione transferase (GST) E2 activity is associated with DDT resistance in the mosquito Anopheles gambiae. The search for chemomodulators that inhibit the function of AgGSTE2 would enhance the insecticidal activity of DDT. Therefore, we examined the interaction of novel natural plant products with heterologously expressed An. gambiae GSTE 2 in vitro. Five of the ten compounds, epiphyllocoumarin (Tral-1), knipholone anthrone, isofuranonaphthoquinones (Mr 13/2, Mr13/4) and the polyprenylated benzophenone (GG1) were shown to be potent inhibitors of AgGSTE2 with IC(50) values of 1.5 microM, 3.5 microM, 4 microM, 4.3 microM and 4.8 microM respectively. Non-competitive inhibition was obtained for Tral 1 and GG1 with regards to GSH (K(i) of 0.24 microM and 0.14 microM respectively). Competitive inhibition for Tral1 was obtained with CDNB (K(i) = 0.4 microM) whilst GG1 produced mixed type of inhibition. The K(i) and K(i)' for GSH for Tral-1 and GG1 were 0.2 microM and 0.1 microM respectively. These results suggest that the novel natural plant products, particularly Tral-1, represent potent AgGSTE2 in vitro inhibitors.
Muleya
Victor
V
Biomolecular Interactions Analyses Group, Department of Biochemistry, University of Zimbabwe, Harare, Zimbabwe.
Hayeshi
Rose
R
Ranson
Hilary
H
Abegaz
Berhanu
B
Bezabih
Merha-Tibeb
MT
Robert
Metuno
M
Ngadjui
Boneventure T
BT
Ngandeu
Francois
F
Mukanganyama
Stanley
S
D000818:Animals; D000852:Anopheles / Q000201:enzymology*; D001688:Biological Products / Q000494:pharmacology*; D003634:DDT / Q000494:pharmacology; D004791:Enzyme Inhibitors; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors*; D007305:Insecticide Resistance / Q000187:drug effects; D010944:Plants / Q000737:chemistry
D001688:Biological Products; D004791:Enzyme Inhibitors; D003634:DDT; D005982:Glutathione Transferase