Majucin-type Illicium sesquiterpenes with potent neurotrophic activity are considered to be promising candidates for the treatment of various neurodegenerative disease. Owing to the low-abundance metabolites in Illicium genus, there are few studies on their structural modifications, structure-activity relationships, and pharmacophoric motif. Herein, structural modifications were conducted on the hydroxyl groups at C-3 and C-6 positions of two majucin-type compounds neomajucin (1) and majucin (2), and 39 neomajucin/majucin based esters were synthesized and evaluated for their neurite outgrowth-promoting activities. Among all the target derivatives, compounds 1a, 1j, 1r, 2b, 2d, 3a, 3b, 3d and 3h displayed more potent neurite outgrowth-promoting activity than their precursors. Some interesting structure–activity relationships (SARs) were also observed. Moreover, compound 1a showed good neuroprotective effect on MPP⁺-induced PC12 cell damage. Finally, compounds 1a and 3a exhibited relatively no cytotoxicity to normal human H9C2 cardiac cells. This work will shed light on the development of neomajucin/majucin derivatives as potential neurotrophic agents.

具有强神经营养活性的Majucin 型八角萜类化合物被认为是治疗各种神经退行性疾病的有希望的候选者。由于八角属的代谢产物丰度较低，对其结构修饰、构效关系和药效基序的研究较少。在此，对两种majucin 型化合物neomajucin ( 1 ) 和majucin ( 2 )的C-3 和C-6 位的羟基进行了结构修饰，合成了39 种neomajucin/majucin 基酯并评估了它们的神经突生长。 - 宣传活动。在所有目标衍生物中，化合物1a、1j、1r、2b、2d、3a、3b、3d和3h显示出比它们的前体更有效的神经突生长促进活性。还观察到了一些有趣的结构-活性关系 (SAR)。此外，化合物1a对MPP ⁺诱导的PC12细胞损伤表现出良好的神经保护作用。最后，化合物1a和3a对正常人 H9C2 心肌细胞没有表现出细胞毒性。这项工作将阐明作为潜在神经营养剂的新马朱素/马朱辛衍生物的开发。