Neuritogenic activities of 1-alkyloxygenipins.
We designed 1-alkyloxygenipins with the aim of improving the stability of genipins based on the structural and electronic properties of genipins, and prepared 1-alkyloxygenipins and examined their neuritogenic activities in PC12h cells. All genipin-derivatives exhibited electronic properties similar to those of genipin and induced significant neurite outgrowth. These compounds will be classified as nitric oxide synthase (NOS) activators (neuritogenic active compounds) since their lowest unoccupied molecular orbital (LUMO)-energies are similar to that of tetrahydrobiopterin (H4B). (1R)-isoPropyloxygenipin showed activity comparable to that of genipin, and unlike the parent compound genipin, it was found to be physiologically stable in rat liver homogenate.
Suzuki
Hirokazu
H
Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3 Kanagawa-machi, Kanazawa, Ishikawa 920-1181, Japan. h-suzuki@hokuriku-u.ac.jp
Yamazaki
Matsumi
M
Chiba
Kenzo
K
Uemori
Yoshio
Y
Sawanishi
Hiroyuki
H
D000818:Animals; D002460:Cell Line; D004355:Drug Stability; D057889:Iridoid Glycosides; D039823:Iridoids / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D016501:Neurites / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar
C569486:1-isopropyloxygenipin; D057889:Iridoid Glycosides; D039823:Iridoids; C007834:genipin; D019001:Nitric Oxide Synthase