Design, synthesis and biological evaluation of novel N-nitrophenyl derivatives based on the structure of acetohydroxyacid synthase

Acetohydroxyacid synthase (AHAS, EC: 2.2.1.6) is a target for the development of novel herbicides. Two series of N-nitrophenyl derivatives, type-A and type-B, were designed and synthesized based on the active site of the AHAS structure. All the structures of newly prepared compounds were thorough characterized by IR, and H-1 NMR spectrums. The IC50 values of all synthesized target compounds against AHAS enzyme and EC50 values for herbicidal activity against Brassica campestris L., Amaranthus mangostanus L. and Sorghum sudanense were determined. The bioactive assay results showed that the type-B compounds exhibited highly improved inhibitory activity against the AHAS enzyme and the tested plants comparing to type-A compounds. The IC50 values of most type-B compounds against the AHAS enzyme were between 25-177 mu M. The EC50 values of several type-B compounds against Sorghum sudanense reached 5.0 mg/L. The differences in the biological activity between type A and type-B compounds were attributed to two structural features - the orthogonal bend at the N-nitro amides group and the common plane structure of another phenyl with chain bridge. With the structure of the target compounds and the IC50 values for AHAS enzyme, a statistically significant CoMFA model with high predict abilities (q(2) = 0.606, r(2) = 0.982, N = 4, SEE = 0.058, F = 280.255) was obtained, and its reliability was verified. The model will provide a theoretical basis for the further structural optimization.