A series of quaternary aminium salts (QAS) have been synthesized in reaction of n-bromoalkyl 2’,3’,4’,6’-tetra-O-acetyl-β-d-glycopyranoside and n-bromoalkyl 2’,3’,4’,6’-tetra-O-acetyl-α-d-glycopyranoside with tertiary amines: pyridine and trimethylamine.
In order to examine genotoxic potential of newly synthesized N-[n-(d-glycopyranosyloxy)alkyl]aminium salts, we used two different bacterial mutagenicity assays. First of them, known as an Ames test, employs histidine dependent Salmonella typhimurium strains and is recognized as the most commonly used short-term bacterial mutagenicity assay, not only for scientific purposes, but also applied in analysis of newly introduced chemicals by regulatory agencies. In the second assay marine Vibrio harveyi A16 dim mutant is used. Upon the addiction of a genotoxic compound a particular fraction of bacteria regain bioluminescence ability, which serves as a measure of a mutagenic effect.
One of analyzed compounds, N-[11-(2’,3’,4’,6’-tetra-O-acetyl-α-d-glucopyranosyloxy)undecyl]-N,N,N-trimethylaminium bromide exhibited pronounced mutagenic activity in the Ames test. For two other compounds, N-[11-(β-d-glucopyranosyloxy)undecyl]pyridinium bromide and N-[2-(2’,3’,4’,6’-tetra-O-acetyl-β-d-galactopyranosyloxy)ethyl]pyridinium bromide, a weak mutagenic effect in the Ames test was observed. Remaining compounds were assessed as non-mutagenic. On the other hand, V. harveyi bioluminescence assay demonstrated a pronounced mutagenic effect in a broad range of compounds concentrations, which suggest higher sensitivity of V. harveyi test in comparison to the Ames test.
These findings demonstrate that N-[n-(d-glycopyranosyloxy)alkyl]aminium salts can be genotoxic and reveal the need for their further profound testing, especially with test systems which can provide high sensitivity, such as V. harveyi bioluminescence assay.
Acknowlegdements:
This work was partially financed by grant DS/530-8451-D193-12.
The publication is partially financed from European Social Fund.
