关键词: KARI酶, 抑制剂, 酰胺类化合物, 生物活性

Abstract: Ketol-acid reductoisomerase(KARI) is a promising target for the design of herbicides, however, there are only few literatures about the molecular design of KARI inhibitors. In this paper, on the basis of the reported 0.165 nm high resolution crystal structure of spinach KARI complex, 279 molecules with a low binding energy toward KARI were obtained from MDL/ACD 3D database searching by program DOCK 4.0. According to the structural information of 279 molecules provided, some amide compounds were synthesized. The bioassay results show that most of these amides had an inhibitory activity to rice KARI at a test concentration of 200 μg/mL, Among the eight amides synthesized, compounds 1 and 6 showed 57.4% and 48.1% inhibitory activity to KARI. The herbicidal activities of these amides were further investigated on di-cotyledonous rape(Brassica campestris) and mono-cotyledonous barnyardgrass(Echinochloa crusgalli). Compounds 1 and 6 were more favorable than others and showed 52.0% and 72.6% inhibitory activity on rape root at 100 μg/mL concentration, which was correlated with their in vitro activity to KARI. These amides KARI inhibitors designed can be further optimized for finding more potent KARI inhibitors and herbicide candidates as well.

Key words: KARI, Inhibitor, Amide compound, Biological activity