Neuritogenic Activities of 1-Alkyloxygenipins

• Published in: Chemical & Pharmaceutical Bulletin Vol. 58; no. 2; pp. 168 - 171
• Main Authors: Suzuki, Hirokazu, Yamazaki, Matsumi, Chiba, Kenzo, Uemori, Yoshio, Sawanishi, Hiroyuki
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01-02-2010; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: 1-isopropyloxygenipin; Animals; Cell Line; Drug Stability; genipin; Iridoid Glycosides; Iridoids - chemical synthesis; Iridoids - chemistry; Iridoids - metabolism; Iridoids - pharmacology; Liver - metabolism; Models, Molecular; Molecular Structure; Neurites - metabolism; neuritogenic activity; neuronal nitric oxide synthase; Neurons - cytology; Neurons - drug effects; Nitric Oxide Synthase - metabolism; Protein Binding; Rats; Rats, Wistar; tetrahydrobiopterin
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.58.168

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.