Rare-Earth Metal Complexes of the Antibacterial Drug Oxolinic Acid: Synthesis, Characterization, DNA/Protein Binding and Cytotoxicity Studies

“Drug repositioning” is a current trend which proved useful in the search for new applications for existing, failed, no longer in use or abandoned drugs, particularly when addressing issues such as bacterial or cancer cells resistance to current therapeutic approaches. In this context, six new complexes of the first-generation quinolone oxolinic acid with rare-earth metal cations (Y3+, La3+, Sm3+, Eu3+, Gd3+, Tb3+) have been synthesized and characterized. The experimental data suggest that the quinolone acts as a bidentate ligand, binding to the metal ion via the keto and carboxylate oxygen atoms; these findings are supported by DFT (density functional theory) calculations for the Sm3+ complex. The cytotoxic activity of the complexes, as well as the ligand, has been studied on MDA-MB 231 (human breast adenocarcinoma), LoVo (human colon adenocarcinoma) and HUVEC (normal human umbilical vein endothelial cells) cell lines. UV-Vis spectroscopy and competitive binding studies show that the complexes display binding affinities (Kb) towards double stranded DNA in the range of 9.33 × 104 − 10.72 × 105. Major and minor groove-binding most likely play a significant role in the interactions of the complexes with DNA. Moreover, the complexes bind human serum albumin more avidly than apo-transferrin.

Oxidation of Florfenicol and Oxolinic Acid in Seawater by Ozonation

There has been an increase in the use of antibiotics by the aquaculture industry in marine aquaculture for the prevention of diseases in fish. Antibiotics in the water discharged into the sea without treatment can cause disturbances to the marine ecosystem. Therefore, there is a need for research on how the removal of antibiotics used in aquaculture can be achieved. In this study, the removal of two types of antibiotics (florfenicol, FF, and oxolinic acid, OA) used in the aquaculture industry, by ozonation, was evaluated. Currently, there is a lack of research studies on FF and OA removal from seawater by ozonation. Seawater ozonation shows a significantly different oxidation mechanism as compared to that of freshwater. The high amount of Br− in seawater (60 mg/L) allows for a rapid reaction with ozone to produce bromine (HOBr/OBr−) at a rate of 160 M−1s−1. To predict the removal efficiency of antibiotics by ozone and bromine, the species-specific rate constants for the reaction of FF and OA with ozone and bromine were determined. The predicted removal efficiencies of FF and OA using measured rate constants were verified by the ozonation process in water containing bromide ions in similar concentrations as in seawater. The result for FF indicated less than 10% removal during 20 min, with the rate constants of FF with ozone and bromine being 3.2 M−1s−1 and 3.5 M−1s−1, respectively. However, the removal of OA using ozonation was approximately 99% or higher within 90 s. In the presence of bromide ions, approximately 60% of OA was removed by trace ozone within 15 s, and approximately 30% of OA was removed by the generated bromine after 15 s. Comparing the removability of FF and OA used in aquaculture by ozone, it was observed that FF was more difficult to remove because of its low reaction rate constant. Meanwhile, the reaction rates of OA with ozone and bromine were 2.4 × 103 M−1s−1 and 4.0 × 102 M−1s−1, respectively. At the beginning of the reaction, OA was removed by the trace ozone. Subsequently, OA was removed by the generated bromine after the ozone was decomposed.

Antibiotic-Induced Perturbations Are Manifested in the Dominant Intestinal Bacterial Phyla of Atlantic Salmon

The intestinal microbiota of certain farmed fish are often exposed to antimicrobial substances, such as antibiotics, that are used to prevent and treat bacterial diseases. Antibiotics that kill or inhibit the growth of harmful microbes can rapidly alter intestinal microbial diversity and composition, with potential effects on the host health. In this study, we have elucidated the impact of two antibiotics, florfenicol and oxolinic acid, by employing a high-throughput 16S rRNA gene amplicon sequencing technique on the distal and mid intestinal microbial communities of Atlantic salmon (Salmo salar). For this, Atlantic salmon were offered diets with or without antibiotics. We then investigated the bacterial communities in the intestinal mucus of the fish. Our results showed that antibiotic exposure shifts the intestinal microbial profile differentially. In addition, the bacterial compositions of the control and antibiotic-fed groups were significantly different. Antibiotic feeding altered the composition and abundance of the dominant bacterial phyla, namely Proteobacteria, Actinobacteria, Firmicutes, Spirochaetes, Bacteroidetes, Tenericutes, and Thermotogae. The bacterial association network analysis also indicated the differential pattern of co-occurrence of bacteria in the three study groups. The results regarding the differences in the structure and association of the intestinal microbiota of Atlantic salmon after florfenicol and oxolinic acid feeding can be employed to attenuate the adverse effects of antibiotic feeding on fish.