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Synthesis of Stable Genipin Derivatives and Studies of Their Neuroprotective Activity in PC12 Cells
Author(s) -
Luo Jun,
Wang Rikang,
Huang Zhao,
Yang Jian,
Yao Xinsheng,
Chen Heru,
Zheng Wenhua
Publication year - 2012
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201200258
Subject(s) - genipin , neuroprotection , chemistry , pharmacology , combinatorial chemistry , biochemistry , biology , chitosan
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.