Phytotoxicity of aminobisphosphonates targeting both δ 1 -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 delta(1)-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-dibromophenyl aminomethylenebis phosphonic acid (Br(2)PAMBPA), 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 Br(2)PAMBPA, 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. (C) 2016 Society of Chemical Industry