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Synthesis and phospholipase C inhibitory activity of D609 diastereomers
Author(s) -
GonzálezRoura Albert,
Casas Josefina,
Llebaria Amadeu
Publication year - 2002
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/s1145-002-0908-0
Subject(s) - diastereomer , xanthate , chemistry , stereochemistry , moiety , phospholipase c , enzyme , biochemistry , organic chemistry
The potassium xanthate D609 is widely accepted as a selective inhibitor of PC‐specific phospholipase C (PC‐PLC). The tricyclo[5.2.1.0 2,6 ]decane skeleton present in D609 can lead to four diastereomeric paris, but the diastereoselectivity of PC‐PLC inhibition has never been reported. In this article, the synthesis of racemic D609 diastereomers and that of other xanthates, as well as their inhibitory effect on PC‐PLC is reported. All xanthates obtained were competitive inhibitors of PC‐PLC from Bacillus cereus (PLC Bc ). No significant differences were found in the activity of D609 diastereomers ( K i 13–17 μM), suggesting the absence of a diastereochemical control of the enzyme by xanthate inhibitors. This result was confirmed after obtaining other potassium xanthates differing from D609 in the aliphatic chain. Among them, the potassium O‐n ‐decenylxanthate was the most active inhibitor of PLC Bc ( K i 10 μM). These data indicate that the essential structural requirements for PLC Bc in vitro inhibition by xanthates are the presence of a Zn‐chelating dithiocarbonate head and a sufficiently hydrophobic aliphatic moiety.