Phytotoxicity of aminobisphosphonates targeting both δ1-pyrroline-5-carboxylate reductase and glutamine synthetase.
BACKGROUND
Dual-target inhibitors may contribute to the management of herbicide-resistant weeds and avoid or delay the selection of resistant biotypes. Some aminobisphosphonates inhibit the activity of both glutamine synthetase and δ1-pyrroline-5-carboxylate (P5C) reductase in vitro, but the relevance of the latter in vivo has yet to be proven. This study aimed at demonstrating that these compounds can also block proline synthesis in planta.


RESULTS
Two aminophosphonates, namely 3,5-dichlorophenylamino-methylenebisphosphonic acid and 3,5-dibromophenylaminomethylenebis phosphonic acid (Br2PAMBPA), showed inverse effectiveness against the two partially purified target enzymes from rapeseed. The compounds showed equipotency in inhibiting the growth of rapeseed seedlings and cultured cells. The analysis of amino acid content in treated cells showed a strong reduction in glutamate and glutamate-related amino acid pools, but a milder effect on free proline. In the case of Br2PAMBPA, toxic P5C levels accumulated in treated seedlings, proving that the inhibition of P5C reductase takes place in situ.


CONCLUSIONS
Phenyl-substituted aminobisphosphonates may be regarded as true dual-target inhibitors. Their use to develop new active principles for crop protection could consequently represent a tool to address the problem of target-site resistance among weeds. © 2016 Society of Chemical Industry.
Department of Life Science and Biotechnology, University of Ferrara, Ferrara, Italy.
Samuele
S
Giberti
Department of Life Science and Biotechnology, University of Ferrara, Ferrara, Italy.
Michele
M
Bertazzini
Department of Life Science and Biotechnology, University of Ferrara, Ferrara, Italy.
Mattia
M
Liboni
Department of Bioorganic Chemistry, Wrocław University of Technology, Wrocław, Poland.
Łukasz
Ł
Berlicki
Department of Bioorganic Chemistry, Wrocław University of Technology, Wrocław, Poland.
Paweł
P
Kafarski
Department of Life Science and Biotechnology, University of Ferrara, Ferrara, Italy.
Giuseppe
G
Forlani
D029741:Brassica rapa / Q000187:drug effects* / Q000201:enzymology; D004164:Diphosphonates / Q000494:pharmacology*; D005974:Glutamate-Ammonia Ligase / Q000037:antagonists & inhibitors*; D006540:Herbicides; D011762:Pyrroline Carboxylate Reductases / Q000037:antagonists & inhibitors*; D036226:Seedlings / Q000187:drug effects / Q000201:enzymology
D004164:Diphosphonates; D006540:Herbicides; D011762:Pyrroline Carboxylate Reductases; D005974:Glutamate-Ammonia Ligase
P5C reductase; amino acid biosynthesis inhibitors as herbicides; derivatives of aminomethylenebisphosphonic acid; glutamine synthetase; multiple targets; phytotoxicity