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Stereoselective Reduction of 1‐ O ‐Isopropyloxygenipin Enhances Its Neuroprotective Activity in Neuronal Cells from Apoptosis Induced by Sodium Nitroprusside
Author(s) -
Wang Rikang,
Yang Jian,
Liao Sufen,
Xiao Gaokeng,
Luo Jun,
Zhang Lang,
Little Peter J.,
Chen Heru,
Zheng Wenhua
Publication year - 2014
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.201400051
Subject(s) - neuroprotection , sodium nitroprusside , genipin , chemistry , stereoselectivity , apoptosis , pharmacology , stereochemistry , biochemistry , medicine , organic chemistry , nitric oxide , catalysis , chitosan
Genipin is a Chinese herbal medicine with both neuroprotective and neuritogenic activity. Because of its unstable nature, efforts have been to develop more stable genipin derivatives with improved biological activities. Among the new compounds reported in the literature, (1 R )‐isopropyloxygenipin (IPRG001) is a more stable but less active compound compared with the parent, genipin. Here, two new IPRG001 derivatives generated by stereoselective reduction of the C 6 =C 7 double bond were synthesized. The 1 R and 1 S isomers of (4a S ,7 S ,7a S )‐methyl‐7‐(hydroxymethyl)‐1‐isopropoxy‐1,4a,5,6,7,7a‐hexahydrocyclopenta[ c ]pyran‐4‐carboxylate ( CHR20 and CHR21 ) were shown to be very stable both in high‐glucose cell culture medium and in mice serum at 37 °C. Evaluation using an MTT assay and Hoechst staining showed that CHR20 and CHR21 promote the survival of rat adrenal pheochromocytoma (PC12) and retinal neuronal (RGC‐5) cells from injury induced by sodium nitroprusside (SNP). The neuroprotective effects of CHR20 and CHR21 were greater than both isomers of IPRG001, the parent compounds. These results indicate that reduction of 1‐ O ‐isopropyloxygenipin enhances its neuroprotective activity without affecting its stability.