Antibacterial Activity of
Sulfamethoxazole Transformation
Products (TPs): General Relevance for Sulfonamide TPs Modified at
the <i>para</i> Position
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Abstract
Sulfonamide
antibiotics undergo transformation in the aquatic environment
through biodegradation, photolysis, or hydrolysis. In this study,
the residual antibacterial activity of 11 transformation products
(TPs) of sulfamethoxazole (SMX) was investigated with regard to their <i>in vitro</i> growth and luminescence inhibition on Vibrio fischeri (30 min and 24 h exposure). Two transformation
products, 4-hydroxy-SMX and <i>N</i><sup>4</sup>-hydroxy-acetyl-SMX,
were synthesized in-house and confirmed by nuclear magnetic resonance
and high-resolution mass spectrometry. Results of individual compound
experiments showed that TPs modified at the <i>para</i> amino
group still exhibit clear antibacterial effects, whereas TPs resulting
from breakdown of the SMX structure lost this mechanism of action.
4-NO<sub>2</sub>- and 4-OH-SMX were found to inhibit growth to a clearly
greater extent than the parent compound, SMX. In contrast, the <i>N</i><sup>4</sup>-acetyl- and <i>N</i><sup>4</sup>-hydroxy-acetyl-derivatives retain less than 10 and 5% of the effect
of SMX on growth and luminescence inhibition, respectively. The effect
of a mixture of <i>para</i>-modified TPs was observed to
be additive. Considering the homologous series of sulfa drugs widely
prescribed and their common mechanism of action, the potential environmental
impact must consider the total amount of sulfonamide antibiotics and
their derivative TPs, which might end up in a water body. Extrapolating
the results obtained here for the <i>para </i>TPs of SMX
to other sulfa drugs and determining the persistence and occurrence
of these compounds in the aquatic environment is required for improved
risk assessment