title: Antibacterial activity of sulfamethoxazole transformation products (TPs): general relevance for sulfonamide TPs modified at the para position.
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 in vitro growth and luminescence inhibition on Vibrio fischeri (30 min and 24 h exposure). Two transformation products, 4-hydroxy-SMX and N(4)-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 para amino group still exhibit clear antibacterial effects, whereas TPs resulting from breakdown of the SMX structure lost this mechanism of action. 4-NO2- and 4-OH-SMX were found to inhibit growth to a clearly greater extent than the parent compound, SMX. In contrast, the N(4)-acetyl- and N(4)-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 para-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 para 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.
authors.affiliation: Karlsruhe Institute of Technology (KIT), Engler-Bunte-Institut , Chair of Water Chemistry and Water Technology, Engler-Bunte-Ring 1, 76131 Karlsruhe, Germany.
authors.forename: Marius
authors.initials: M
authors.lastname: Majewsky
authors.forename: Danny
authors.initials: D
authors.lastname: Wagner
authors.forename: Markus
authors.initials: M
authors.lastname: Delay
authors.forename: Stefan
authors.initials: S
authors.lastname: Bräse
authors.forename: Viviane
authors.initials: V
authors.lastname: Yargeau
authors.forename: Harald
authors.initials: H
authors.lastname: Horn
mesh_terms: D048908:Aliivibrio fischeri / Q000187:drug effects / Q000254:growth & development; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D006868:Hydrolysis; D007700:Kinetics; D008163:Luminescent Measurements; D010782:Photolysis; D013420:Sulfamethoxazole / Q000737:chemistry* / Q000494:pharmacology; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D013449:Sulfonamides; D013420:Sulfamethoxazole