TY - JOUR
T1 - Synthesis of prenylated quinolinecarboxylic acid derivatives and their anti-obesity activities
AU - Kikuchi, Haruhisa
AU - Suzuki, Toshiyuki
AU - Ogura, Masato
AU - Homma, Miwako K.
AU - Homma, Yoshimi
AU - Oshima, Yoshiteru
N1 - Funding Information:
This work was supported in part by a Grant-in-Aid for Scientific Research (No. 25350959 ) from the Ministry of Education, Science, Sports, and Culture of Japan ; Platform for Drug Discovery, Informatics, and Structural Life Science from the Ministry of Education, Culture, Sports, Science, and Technology, Japan ; and the Astellas Foundation for Research on Metabolic Disorders .
Publisher Copyright:
© 2014 Elsevier Ltd. All rights reserved.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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.
AB - 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.
KW - Anti-obesity drugs
KW - Metabolic diseases Quinolinecarboxylate
KW - Mitochondrial uncoupling
KW - Structure-activity relationship
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U2 - 10.1016/j.bmc.2014.11.024
DO - 10.1016/j.bmc.2014.11.024
M3 - Article
C2 - 25496808
AN - SCOPUS:84918803076
SN - 0968-0896
VL - 23
SP - 66
EP - 72
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 1
ER -
