文献类型：期刊文献

英文题名：Structural diversity derivatization and studies on the nematicidal activity of tropane derivatives

作者：Lu, Aoyun[1];Zheng, Yiting[1];Li, Tao[1];Wang, Jiayi[1];Song, Gonghua[1]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, 130 Meilong Rd, Shanghai 200237, Peoples R China

年份：2024

卷号：59

起止页码：108

外文期刊名：PHYTOCHEMISTRY LETTERS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001170881600001)】；

基金：We would like to thank the financial support from the National Key R & D Program (Grant No. 2018YFD0200105) .

语种：英文

外文关键词：Nematicidal activity; Tropane; Lead optimization; Bioisosteric replacement

摘要：Starting from the structure of MDL 72222 and its analogs, the known 5-HT3 receptor antagonists with verified nematicidal activity, we evaluated a diverse array of tropane derivatives that are characterized by the introduction of a variety of pentatomic heterocycles as bioisosteric replacements for the ester moiety of these 5-HT3 receptor antagonists. The in vitro nematicidal activities of all the target compounds were tested against Bursaphelenchus xylophilus and Meloidogyne incognita. A preliminary structure-activity relationship (SAR) investigation demonstrated that the ester functionality in 5-HT3 receptor antagonists could be replaced by a thiazole moiety (analog 5) with modest to good nematicidal activity. Specifically, compound 5bd exhibited excellent nematicidal activity against B. xylophilus with an LC50/72 h of 7.80 mg/L, and 85% mortality at 40 mg/L against M. incognita. Furthermore, a stepwise structural modification of analog 5 led to the discovery of the structurally distinct compound 47b with advanced nematicidal activity, which had an LC50/72 h of 5.96 mg/L against B. xylophilus.