Herbicidal pyridyl derivatives of aminomethylene-bisphosphonic acid inhibit plant glutamine synthetase.

Abstract

A series of aminomethylene-bisphosphonic acid derivatives, previously synthesized and shown to be endowed with herbicidal properties, were evaluated as potential inhibitors of plant glutamine synthetase. The cytosolic form of the enzyme was partially purified from rice cultured cells and assayed in the presence of millimolar concentrations of the compounds by means of three different assay methods, respectively measuring the hemibiosynthetic, the transferase, and the full biosynthetic reactions. Several compounds were found to exert a remarkable inhibition, with I(50) values similar to those obtained under the same conditions with a well-established inhibitor of glutamine synthetase, the herbicide phosphinothricin. Contrary to the reference compound, enzyme kinetics accounted for a reversible inhibition mechanism. The biological activity of the most active derivatives was further characterized by measuring free glutamine levels in cell suspension rice cultures following treatment with the inhibitors. Results confirmed their ability to interfere in vivo with nitrogen metabolism. A preliminary analysis of structure-activity relationship allowed it to be hypothesized that steric rather than electronic factors are responsible for the inhibitory potential of these compounds.