title: Synthesis of stable genipin derivatives and studies of their neuroprotective activity in PC12 cells.
abstract: Modifications at C1, C7, C8, and C10 of genipin were conducted, and the neurotrophic effects of all derivatives were studied. Genipin derivatives 1-4 were obtained in mild to high yield. Compounds 1 and 4 are more stable than genipin if exposed to nucleophiles. All the derivatives display higher neurotrophic activities than genipin. Compound 4 is the most active, with the least optimal dose. Both genipin and 4 up-regulated the activity of nNOS in PC12 cells. The effect of 4 is inhibited not only by 7-NI, a specific inhibitor of nNOS, but also by L-NIO, a specific inhibitor of eNOS; in the case of genipin, its effect is only inhibited by 7-NI. All the results indicate that 4 is a promising lead compound for the development of new drugs in the treatment of neurodegenerative diseases with the ability to address multiple drug targets.
authors: Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, PR China.
authors: Jun
authors: J
authors: Luo
authors: Rikang
authors: R
authors: Wang
authors: Zhao
authors: Z
authors: Huang
authors: Jian
authors: J
authors: Yang
authors: Xinsheng
authors: X
authors: Yao
authors: Heru
authors: H
authors: Chen
authors: Wenhua
authors: W
authors: Zheng
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D032062:Gardenia / Q000737:chemistry; D039823:Iridoids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats
chemical_list: D039823:Iridoids; D018696:Neuroprotective Agents; C000601173:gardenamide A; C007834:genipin; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III