Maria E. Tiritan

Biodegradation of ofloxacin, norfloxacin, and ciprofloxacin as single and mixed substrates by Labrys portucalensis F11.

Fluoroquinolone (FQ) antibiotics are extensively used both in human and veterinary medicine, and their accumulation in the environment is causing an increasing concern. In this study, the biodegradation of the three most worldwide used FQs, namely ofloxacin, norfloxacin, and ciprofloxacin, by the fluoroorganic-degrading strain Labrys portucalensis F11 was assessed. Degradation occurred when the FQs were supplied individually or as mixture in the culture medium, in the presence of an easily degradable carbon source. Consumption of individual FQs was achieved at different extents depending on its initial concentration, ranging from 0.8 to 30xa0μM. For the lowest concentration, total uptake of each FQ was observed but stoichiometric fluoride release was not achieved. Intermediate compounds were detected and identified by LC-MS/MS with a quadrupole time of flight detector analyzer. Biotransformation of FQs by L. portucalensis mainly occurred through a cleavage of the piperazine ring and displacement of the fluorine substituent allowing the formation of intermediates with less antibacterial potency. FQ-degrading microorganisms could be useful for application in bioaugmentation processes towards more efficient removal of contaminants in wastewater treatment plants.

New chiral derivatives of xanthones: Synthesis and investigation of enantioselectivity as inhibitors of growth of human tumor cell lines

A highly efficient and practical methodology for synthesis of new chiral derivatives of xanthones (CDXs) in enantiomerically pure form has been developed. According to this approach, thirty CDXs (3-32) were synthesized by coupling a carboxyxanthone (1) and a carboxymethoxyxanthone (2) with both enantiomers of commercially available chiral building blocks, namely six amino alcohols, one amine and one amino ester. The activation of the carboxylic acid group of the xanthonic scaffold was carried out with the coupling reagent O-(benzotriazol-1-yl)-N-N-N-N-tetramethyluronium tetrafluoroborate (TBTU), in the presence of a catalytic amount of TEA in anhydrous THF. The coupling reactions with the chiral blocks were performed at room temperature with short reactions times, excellent yields (ranging from 94% to 99%), and very high enantiomeric excess. The synthesized CDXs were evaluated for their effect on the in vitro growth of three human tumor cell lines, namely A375-C5 (melanoma), MCF-7 (breast adenocarcinoma), and NCI-H460 (non-small cell lung cancer). The most active compound was CDX 15 being active in all human tumor cell lines with values of GI50 of 32.15±2.03μM for A375-C5, 22.55±1.99μM for MCF-7, and 14.05±1.82μM for NCI-H460. Nevertheless, some CDXs showed cell-type selectivity. Furthermore, the growth inhibitory effects, in some cases, demonstrated to be depending on the stereochemistry of the CDXs. An interesting example was observed with the enantiomers 3 and 4, which demonstrated high enantioselectivity for MCF-7 and NCI-H460 cell lines. It can be inferred that the effects on the growth of the human tumor cell lines can be ascribed not only to the nature and positions of substituents on the xanthonic scaffold but also to the stereochemistry of the CDXs. Some considerations regarding structure-activity relationship within this class of compounds will be highlighted.