title: Synthesis of prenylated quinolinecarboxylic acid derivatives and their anti-obesity activities.
abstract: 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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-yama, Aoba-ku, Sendai 980-8578, Japan. Electronic address: hal@mail.pharm.tohoku.ac.jp.
authors.forename: Haruhisa
authors.initials: H
authors.lastname: Kikuchi
authors.affiliation: Fukushima Medical University, School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Fukushima Medical University, School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Ogura
authors.affiliation: Fukushima Medical University, School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Miwako K
authors.initials: MK
authors.lastname: Homma
authors.affiliation: Fukushima Medical University, School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Homma
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-yama, Aoba-ku, Sendai 980-8578, Japan.
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Oshima
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D054876:Prenylation; D011805:Quinolinic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014475:Uncoupling Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D019440:Anti-Obesity Agents; D011805:Quinolinic Acids; D014475:Uncoupling Agents
keywords: Anti-obesity drugs; Metabolic diseases; Mitochondrial uncoupling; Quinolinecarboxylate; Structure–activity relationship