1246887-09-1Relevant articles and documents
Cytoprotective effects evaluation of a novel danshensu derivative DEX-018 against oxidative stress injury in HUVECs
He, Kun,Hu, Zhenlin,Li, Yi,Tao, Yulong,Wang, Tingfang,Xu, Chunfang,Xu, Honglei,Zhang, Chuan
, p. 801 - 809 (2020)
Ischemic heart disease (IHD) is one of the most common cardiovascular diseases with high morbidity and mortality. Danshensu (DSS) is widely used in the treatment of coronary heart disease. In this study, the carboxy group of DSS was esterified with edaravone to synthesize the novel DSS derivative DEX-018 to achieve a synergistic protective effect and overcome the structural deficiency of DSS. The pharmacological effect of DEX-018 against tert-butyl hydrogen peroxide (t-BHP) induced oxidative damage in human umbilical vein endothelial cells (HUVECs) was evaluated. The results demonstrated that pretreatment with DEX-018 significantly increased cell viability and superoxide dismutase (SOD) activity and decreased the lactate dehydrogenase (LDH) leakage rate, malondialdehyde (MDA) level and intracellular reactive oxygen species (ROS) level. In addition, DEX-018 inhibited cell apoptosis and reversed the expression of apoptosis-related proteins (Bcl-2, Bax, and caspase-3) in HUVECs stimulated by t-BHP. Further study on the mechanism of DEX-018 revealed that the expression of p-Akt and p-extracellularsignal-regulated kinase 1/2 (ERK1/2) was increased, which suggested that DEX-018 may protect HUVECs against t-BHP induced oxidative injury via the Akt and ERK1/2 signaling pathways. To further validate the correlation, CCK8 was used to detect cell viability after treatment with DEX-018 plus Akt inhibitor (MK2206) and phosphadylinositol 3-kinase (PI3K) inhibitor (LY294002). Compared with DEX-018 alone, MK2206 or LY294002 significantly decreased cell viability of HUVECs, indicating that the protective effect of DEX-018 against t-BHP induced oxidative injury was significantly weakened. It was further verified that the antioxidant and anti-apoptotic effects of DEX-018 were partly related to the PI3K–Akt signaling pathway.
Explorations of caffeic acid derivatives: Total syntheses of rufescenolide, yunnaneic acids C and D, and studies toward yunnaneic acids A and B
Griffith, Daniel R.,Botta, Lorenzo,St. Denis, Tyler G.,Snyder, Scott A.
, p. 88 - 105 (2014/01/17)
Yunnaneic acids A-D, isolated from the roots of Salvia yunnanensis, are hexameric (A and B) and trimeric (C and D) assemblies of caffeic acid that feature an array of synthetically challenging and structurally interesting domains. In addition to being caffeic acid oligomers, yunnaneic acids A and B are formally dimeric and heterodimeric adducts of yunnaneic acids C and D. Herein we report the first total syntheses of yunnaneic acids C and D featuring the formation of their bicyclo[2.2.2]octene cores in a single step from simple precursors via an oxidative dearomatization/Diels-Alder cascade that may have biogenetic relevance. In addition, exploitation of the key intermediate resulting from this cascade reaction has enabled rapid access to the structurally related caffeic acid metabolite rufescenolide through an unexpected Lewis acid-mediated reduction. Finally, we report the results of extensive model studies toward forming the dimeric yunnaneic acids A and B. These explorations indicate that the innate reactivities of the monomeric fragments do not favor spontaneous formation of the desired dimeric linkages. Consequently, enzymatic involvement may be required for the biosynthesis of these more complex family members.
