Two goitrogenic 1,3-oxazolidine-2-thione derivatives from Brassicales taxa: Challenging identification, occurrence and immunomodulatory effects

• Published in: Food and chemical toxicology 2017-12, Vol.110, p.94-108
• Main Authors: Radulović, Niko S., Todorovska, Milica M., Zlatković, Dragan B., Stojanović, Nikola M., Randjelović, Pavle J.
• Format: Article
• Language: English
• Subjects: 1,3-Oxazolidine-2-thione; 5,5-Dimethyl-1,3-oxazolidine-2-thione; 5-Phenyl-1,3-oxazolidine-2-thione; Animals; Brassicaceae - chemistry; Chromatography, Gas; Cruciferous foodstuff; Goitrogenic volatile products; Humans; Immunologic Factors - chemistry; Immunologic Factors - isolation & purification; Immunologic Factors - pharmacology; Inflammation - drug therapy; Macrophages; Magnetic Resonance Spectroscopy; Molecular Structure; Oxazoles - chemistry; Oxazoles - isolation & purification; Oxazoles - pharmacology; Plant Extracts - chemistry; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Rats; Rats, Wistar; Stereoisomerism; Thiones - chemistry; Thiones - isolation & purification; Thiones - pharmacology
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2017.10.005

1,3-Oxazolidine-2-thione derivatives are glucosinolate-related food constituents known to impart (thyreo)toxic properties to some cruciferous vegetables. In this work, 5,5-dimethyl-1,3-oxazolidine-2-thione and (-)-(R)-5-phenyl-1,3-oxazolidine-2-thione, known goitrogens, were isolated from Draba lasiocarpa Rochel (Brassicaceae) and Reseda luteola L. (Resedaceae), respectively, and were fully spectrally characterized. Subsequently, the occurrence of the two 1,3-oxazolidine-2-thiones was verified in six additional taxa out of in total 78 screened Serbian Brassicales taxa. The stereochemistry of 5-phenyl-1,3-oxazolidine-2-thione was inferred from nuclear magnetic resonance experiments with a chiral lanthanide-shift reagent, employed in this work for the first time for this type of compounds. Unexpectedly, during gas chromatography, 5-phenyl-1,3-oxazolidine-2-thione underwent an unreported thermal core isomerization (1,3-oxazolidine-2-thione to 1,3-thiazolidine-2-one). These goitrogenic volatile glucosinolate products were tested for their effect on rat macrophage viability (three assays) and nitric oxide production. It was shown that the compounds displayed different levels of cytotoxicity. All tested compounds caused a significant lactate dehydrogenase leakage, but only (R)-5-phenyl-1,3-oxazolidine-2-thione statistically significantly reduced macrophage mitochondrial activity, whereas the racemic 5-phenyl-1,3-oxazolidine-2-thione and 5,5-dimethyl-1,3-oxazolidine-2-thione had little or no effect. Again only (R)-5-phenyl-1,3-oxazolidine-2-thione exerted nitric oxide production-inhibiting properties, suggesting the higher immunomodulatory potential of this enantiomer compared with its antipode and racemic mixture. [Display omitted] •5,5-Dimethyl-1,3-oxazolidine-2-thione (1) and 5-phenyl-1,3-oxazolidine-2-thione (2) were isolated from two Brassicales taxa.•Plant autolyzates (159 samples, including edible crucifers) were screened for these toxic (goitrogenic) food constituents.•Compounds 1 and 2 showed immunomodulatory activity by affecting the viability and NO-producing ability of macrophages.•Both 1,3-oxazolidine-2-thiones readily reacted with NO+ species generating products that themselves could yield NO.•Enantiomers of 2 were differentiated by a newly developed NMR-based methodology and its problematic GC behavior clarified.