Allium chemistry: synthesis, natural occurrence, biological activity, and chemistry of Se-alk(en)ylselenocysteines and their gamma-glutamyl derivatives and oxidation products.
Syntheses are reported for gamma-glutamyl Se-methylselenocysteine (Sa), selenolanthionine (16), Se-1-propenylselenocysteine (Gd), Se-2-methyl-2-propenyl-L-selenocysteine (6e), and Se-2-propynyl-L-selenocysteine (6f). Oxidation of 8a and Se-methylselenocysteine (Ga) gives methaneseleninic acid (24), characterized by X-ray crystallography, and dimethyl diselenide (25). Oxidation of Se-2-propenyl-L-selenocysteine (6c) gives allyl alcohol and 3-seleninoalanine (22). Compound 22 is also formed on oxidation of 16 and selenocystine (4). Oxidation of 6d gives 2-[(E,Z)-1-propenylseleno]propanal (36). These oxidations occur by way of selenoxides, detected by chromatographic and spectroscopic methods. The natural occurrence of many of the Se-alk(en)ylselenocysteines and their gamma-glutamyl derivatives and oxidation products is discussed. Three homologues of the potent cancer chemoprevention agents 6a and 6c, namely 6d-f, were evaluated for effects on cell growth, induction of apoptosis, and DNA-damaging activity using two murine mammary epithelial cell lines. Although each compound displays a unique profile of activity, none of these compounds (Gd-f) is likely to exceed the chemopreventive efficacy of selenocysteine Se-conjugates Ga and 6c.
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Department of Chemistry, State University of New York, Albany 12222, USA. eb801@csc.albany.edu
Birringer
M
M
Jiang
W
W
Nakahodo
T
T
Thompson
H J
HJ
Toscano
P J
PJ
Uzar
H
H
Zhang
X
X
Zhu
Z
Z
D000490:Allium / Q000737:chemistry*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D018360:Crystallography, X-Ray; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D005260:Female; D008321:Mammary Glands, Animal / Q000166:cytology / Q000187:drug effects; D051379:Mice; D010084:Oxidation-Reduction; D017279:Selenocysteine / Q000031:analogs & derivatives / Q000032:analysis / Q000737:chemistry* / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; C428345:se-1-propenylselenocysteine; C428346:se-2-methyl-2-propenyl-selenocysteine; D017279:Selenocysteine