当前位置: X-MOL 学术Eur. J. Med. Chem. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Novel lipid-mimetic prodrugs delivering active compounds to adipose tissue
European Journal of Medicinal Chemistry ( IF 6.0 ) Pub Date : 2017-04-21 04:27:50
Andrea Mattarei, Andrea Rossa, Veronica Bombardelli, Michele Azzolini, Martina La Spina, Cristina Paradisi, Mario Zoratti, Lucia Biasutto

Obesity and associated pathologies are a dramatically growing problem. New therapies to prevent and/or cure them are strongly needed. Adipose tissue is a logical target for pharmacological intervention, since it is now recognized to exert an important endocrine function, secreting a variety of adipokines affecting, for example, adiposity and insulin resistance. This proof of principle work focuses on the development of novel lipid-mimetic prodrugs reaching fat deposits by the same lymphatic absorption route followed by dietary triglycerides. Pterostilbene, a natural phenolic compound with potential anti-obesity effects, was used as model “cargo”, attached via a carbamate group to an ω-aminodecanoate chain linked to either position 1 or position 2 of the glycerol moiety of synthetic triglycerides. The prodrugs underwent position-selective hydrolysis when challenged with pancreatic lipases in vitro. Pterostilbene-containing triglycerides as well as pterostilbene and its metabolites were present in the adipose tissue of mice fed an obesogenic diet containing one or the other of the derivatives. For the first time this approach is used to deliver an obesity antagonist to the adipose tissue. The results demonstrate the feasibility of delivering active compounds to adipose tissue by reversibly incorporating them into triglyceride-mimetic structures. Upon release in the target site these compounds are expected to exert their pharmacological activity precisely where needed.

中文翻译:

新型脂质模拟前药,可将活性化合物输送至脂肪组织

肥胖症和相关的病理学是一个急剧增长的问题。强烈需要新的疗法来预防和/或治愈它们。脂肪组织是药理学干预的逻辑目标,因为现已认识到脂肪组织发挥重要的内分泌功能,分泌各种影响例如肥胖症和胰岛素抵抗的脂肪因子。这项原理性工作的重点在于开发通过相同的淋巴吸收途径和饮食中的甘油三酸酯达到脂肪沉积的新型类脂模拟前药。紫杉萜是一种具有潜在的抗肥胖作用的天然酚类化合物,被用作“货物”模型,通过氨基甲酸酯基连接到连接到合成甘油三酸酯甘油部分1或2位置的ω-氨基癸酸酯链上。当在体外用胰脂肪酶挑战时,前药经历位置选择性水解。喂食含有一种或另一种衍生物的致肥胖饮食的小鼠的脂肪组织中存在着含萜烯的甘油三酸酯以及萜烯及其代谢产物。首次将这种方法用于将肥胖拮抗剂递送至脂肪组织。结果证明了通过将活性化合物可逆地掺入到甘油三酸酯模拟结构中来将活性化合物递送至脂肪组织的可行性。预期这些化合物在靶位点释放后将在需要的地方精确发挥其药理活性。喂食含有一种或另一种衍生物的致肥胖饮食的小鼠的脂肪组织中存在着含萜烯的甘油三酸酯以及萜烯及其代谢产物。首次将这种方法用于将肥胖拮抗剂递送至脂肪组织。结果证明了通过将活性化合物可逆地掺入到甘油三酸酯模拟结构中来将活性化合物递送至脂肪组织的可行性。预期这些化合物在靶位点释放后将在需要的地方精确发挥其药理活性。喂食含有一种或另一种衍生物的致肥胖饮食的小鼠的脂肪组织中存在着含萜烯的甘油三酸酯以及萜烯及其代谢产物。首次将这种方法用于将肥胖拮抗剂递送至脂肪组织。结果证明了通过将活性化合物可逆地掺入到甘油三酸酯模拟结构中来将活性化合物递送至脂肪组织的可行性。预期这些化合物在靶位点释放后将在需要的地方精确发挥其药理活性。结果证明了通过将活性化合物可逆地掺入到甘油三酸酯模拟结构中来将活性化合物递送至脂肪组织的可行性。预期这些化合物在靶位点释放后将在需要的地方精确发挥其药理活性。结果证明了通过将活性化合物可逆地掺入到甘油三酸酯模拟结构中来将活性化合物递送至脂肪组织的可行性。预期这些化合物在靶位点释放后将在需要的地方精确发挥其药理活性。
更新日期:2017-04-21
down
wechat
bug