Wang J.,Zhou Y.,Wu X.,Zhou X.,Sun Y.,Wu W.,Wang X.
Discovering super-efficient herbicides with novel structures is one of the effective ways to solve the increasingly severe weed resistance problem and meet ecological requirements. In this work, a series of novel bromo- p -hydroxybenzamides were designed based on the molecular hybridization strategy, and rapidly synthesized by one-step amidation reaction, and then characterized by 1 H NMR, 13 C NMR and HRMS. The herbicidal activity assay indicated that most of the target compounds exhibited good-to-excellent inhibition effects on seed germination of two model plants. At a concentration of 100 mg/L, the inhibition rate of 3,5-dibromo- N -(4-bromo-3-chlorophenyl)- p -hydroxybenzamide reached up to 98 and 96% on the roots and stalks of the monocotyledonous barnyard grass ( E. crus-galli ), respectively. 3,5-Dibromo- N -(2-bromophenyl)- p -hydroxybenzamide showed excellent inhibitory activity on the roots and stalks of dicotyledonous rape ( B. napus ) at 100 mg/L, with an inhibitory rate of more than 90%. Furthermore, the concentration was reduced to 1 mg/L, the inhibitory rate of 3,5-dibromo- N -(2-bromophenyl)- p -hydroxybenzamide on the roots of B. napus was still as high as 90%. This work provides a novel molecular scaffold for the development and research of new super-efficient herbicides.
Efficient and mild synthetic routes for bioactive natural product derivatives are of current interest for drug discovery. Herein, on the basis of the pharmacophore hybrid strategy, we report a two-step protocol to obtain a series of structurally novel oleanolic acid (OA)-dithiocarbamate conjugates in mild conditions with high yields. Moreover, biological evaluations indicated that representative compound3eexhibited the most potent and broad-spectrum antiproliferative effects against Panc1, A549, Hep3B, Huh-7, HT-29, and Hela cells with low cytotoxicity on normal cells. In terms of the IC50values, these OA-dithiocarbamate conjugates were up to 30-fold more potent than the natural product OA. These compounds may be promising hit compounds for the development of novel anti-cancer drugs.Keywords:structural modification;oleanolic acid;natural product derivative;dithiocarbamate;hybrid strategy;antitumor activity
危险品化学品经营许可证（带存储）