Synthesis, crystal structure, in vitro acetohydroxyacid synthase inhibition, in vivo herbicidal activity, and 3D-QSAR of new asymmetric aryl disulfides.

Acetohydroxyacid synthase (AHAS; EC 2.2.1.6) is an important bioactive target for the design of environmentally benign herbicides. On the basis of previous virtual screening, 50 asymmetric aryl disulfides containing [1,2,4]triazole groups were synthesized and characterized by (1)H NMR, HRMS, and crystal structure. Compounds I-a, I-b, and I-p show Ki values of 1.70, 4.69, and 5.57 μM, respectively, for wild type Arabidopsis thaliana AHAS (AtAHAS) and low resistance against mutant type AtAHAS W574L. At 100 mg L(-1) concentration, compounds I-a, II-a, and II-b exhibit 86.6, 81.7, and 87.5% in vivo rape root growth inhibition. CoMFA steric and electrostatic contour maps were established, and a possible binding mode was suggested from molecular docking, which provide valuable information to understand the key structural features of these disulfide compounds. To the authors' knowledge, this is the first comprehensive case suggesting that asymmetric aryl disulfides are novel AHAS inhibitors.