Synthesis of Stable Genipin Derivatives and Studies of Their Neuroprotective Activity in PC12 Cells

Abstract

Modifications at C1, C7, C8, and C10 of genipin were conducted, and the neurotrophic effects of all derivatives were studied. Genipin derivatives 1-4 were obtained in mild to high yield. Compounds 1 and 4 are more stable than genipin if exposed to nucleophiles. All the derivatives display higher neurotrophic activities than genipin. Compound 4 is the most active, with the least optimal dose. Both genipin and 4 up-regulated the activity of nNOS in PC12 cells. The effect of 4 is inhibited not only by 7-NI, a specific inhibitor of nNOS, but also by L-NIO, a specific inhibitor of eNOS; in the case of genipin, its effect is only inhibited by 7-NI. All the results indicate that 4 is a promising lead compound for the development of new drugs in the treatment of neurodegenerative diseases with the ability to address multiple drug targets.

Site-selective oxidation, amination and epimerization reactions of complex polyols enabled by transfer hydrogenation

“…In contrast, reaction of this same compound with the catalyst generated from Cy 2 P(CH 2 ) 4 PCy 2 and Ru (DMSO) 4 (OTf) 2 led to a selective isomerization of the allylic alcohol to the corresponding ketone 1q . Genipin underwent oxidation by Ru-2 at the secondary alcohol over the primary allylic alcohol to form lactone 1n directly; prior oxidation to the lactone required protection and deprotection of the primary allylic alcohol 11 .…”

Gardenamide A Protects RGC-5 Cells from H2O2-Induced Oxidative Stress Insults by Activating PI3K/Akt/eNOS Signaling Pathway

“…GA has been shown the effects to protect PC12 cells against serum-deprivation insults [ 12 ]. In the present investigation, it was clearly displayed that H 2 O 2 concentration dependently caused the apoptosis of RGC-5 cells and the increase of ROS and MDA, which are closely related to oxidative stress.…”

“…Previously, we developed a stable genipin derivative gardenamide A (GA) ( Figure 1 ), which was also found in Rothmannia urcelliformis that is widespread in the forests of East Africa, and in the fruit of Gardenia jasminoides [ 11 ]. Like genipin, GA protects PC12 cells from toxicities induced by 6-hydroxydopamine and serum deprivation, respectively, with higher activity [ 12 ]. It is likely that GA can play a role as antioxidant.…”

Design Synthesis of Gardenamide A/Tacrine Hybrids and Their Protection against 6-Hydroxydopamine-Induced Insults in PC12 Cells

“…其前体化合 物 GA 的合成参照文献 [9]. 该路线首先利用京尼平 C-1 和 C-10 羟基反应活泼性的差异, 在弱碱咪唑的作用下, 实现 C-10 羟基的选择性保护, 收率 89%; 从化合物 G-3 至 GA, 文献采用先内酰胺化再脱保护基二甲基叔丁基 硅基(TBS)的两步法, 两步收率分别为 30%和 86%, 总 收率为 25.8%; 本实验对此做了改进, 即内酰胺化后不 分离直接脱 TBS, 两步合并收率提高到 33.8%; 将 GA 中 C-10 羟基用戴斯-马丁试剂(Dess-Martin periodine, DMP) [12,13] 直接氧化, 以 85%的收率得到 DG.…”