The use of molecular modelling for comparison of three possible modes of action of herbicidally active derivatives of aminomethylenebisphosphonic acid

Abstract

( N-Pyridylamino)methylenebisphosphophonic acids constitute a new class of herbicides. Their molecular mechanism of action still awaits determination and so far three enzymes have been identified as possible targets of their action. They are 3-deoxy- d- arabino-heptulosonate-7-phosphate synthase, glutamine synthetase, and farnesyl pyrophosphate synthase. To compare binding properties of the two most active compounds, namely N-2-(5-chloropyridyl)aminomethylenebisphosphonic and N-2-(3-methylo-pyridyl)amino-methylenebisphosphonic acids, they were docked in active sites of three target enzymes using the same molecular modelling program for each enzyme. Inhibition constants estimated by scoring function from program LUDI indicate that the two studied bisphosphonates should be moderate inhibitors of all the three enzymes and thus support postulated multi-target action of these compounds.