Synthesis and Phytotoxic Evaluation of Isatin Derivatives Supported by 3D-QSAR Study.

Concerned about weed infestation, a major threat to food production and herbicide resistance that interferes in the mechanism of action of the main herbicides, we have synthesized eight isatin derivatives using the "Click Chemistry" approach through copper-catalyzed azide-alkyne cycloadditions (CuAAC). Sixteen isatin derivatives were evaluated for their phytotoxic activity against the seed culture of the model plants, and . Six of them showed phytotoxic activity similar to the positive control, trifluralin. Hypocotyl length measurement analysis in revealed that triazole derivative is more active than trifluralin. For , root length measurement analyses revealed that , , , , and were similar to the positive control trifluralin. Three-dimensional quantitative structure-activity relationship (3D-QSAR) comparative molecular field analysis (CoMFA) model construction using the acetolactate synthase (ALS) crystallographic structure displayed p values of predicted inhibitory activity and contour maps revealing sterically bulky groups for , the CF group in ortho, and for , Br in ortho, favoring the inhibitory ALS activity.