Synthesis of prenylated quinolinecarboxylic acid derivatives and their anti-obesity activities
Synthesis of prenylated quinolinecarboxylic acid derivatives and their anti-obesity activities
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DOI：
10.1016/j.bmc.2014.11.024
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发表时间：
2015-01-01
影响因子：
3.5
通讯作者：
Oshima, Yoshiteru
中科院分区：
文献类型：
--
作者：
Kikuchi, Haruhisa;Suzuki, Toshiyuki;Oshima, Yoshiteru
线粒体解偶联是控制各种代谢性疾病和肥胖患者能量代谢的治疗策略之一。PPC-1(1)是从细胞黏菌中分离得到的一种戊烯基喹啉羧酸，在体外具有解偶联活性，在体内具有抗肥胖活性。在本研究中，我们合成了PPC-1(1)及其衍生物，揭示了解偶联活性的构效关系。三戊烯基化化合物18表现出比PPC-1(1)更强的线粒体解偶联活性。化合物18还抑制了小鼠的体重增加，而没有对组织造成损害等不良影响。这些结果表明，化合物18可以作为新型减肥药物的种子化合物。(C)2014爱思唯尔有限公司。保留所有权利。
Mitochondrial uncoupling is one of the therapeutic strategies used to control energy metabolism in various metabolic diseases and in obesity. Ppc-1 (1), a prenylated quinolinecarboxylic acid isolated from cellular slime molds, shows uncoupling activity in vitro and anti-obesity activity in vivo. In this study, we synthesized Ppc-1 (1) and its derivatives, and revealed the structure-activity relationship of uncoupling activities. The triprenylated compound 18 showed mitochondrial uncoupling activity that was more potent than that of Ppc-1 (1). Compound 18 also suppressed weight gain in mice without undesired effects such as lesions on tissues. These results indicate that compound 18 could be used as a seed compound for new anti-obesity drugs. (C) 2014 Elsevier Ltd. All rights reserved.