No abstract

On the basis of X-ray crystallographic studies of the complex of hCA II with 4-(3,4-dihydro-1H-isoquinoline-2-carbonyl)benzenesulfonamide (3) (PDB code 4Z1J ), a novel series of 4-(1-aryl-3,4-dihydro-1H-isoquinolin-2-carbonyl)benzenesulfonamides (23-33) was designed. Specifically, our idea was to improve the selectivity toward druggable isoforms through the introduction of additional hydrophobic/hydrophilic functionalities. Among the synthesized and tested compounds, the (R,S)-4-(6,7-dihydroxy-1-phenyl-3,4-tetrahydroisoquinoline-1H-2-carbonyl)benzenesulfonamide (30) exhibited a remarkable inhibition for the brain-expressed hCA VII (K = 0.20 nM) and selectivity over wider distributed hCA I and hCA II isoforms. By enantioselective HPLC, we solved the racemic mixture and ascertained that the two enantiomers (30a and 30b) are equiactive inhibitors for hCA VII. Crystallographic and docking studies revealed the main interactions of these inhibitors into the carbonic anhydrase (CA) catalytic site, thus highlighting the relevant role of nonpolar contacts for this class of hCA inhibitors.

Pharmaceuticals and personal care products (PPCPs) are abundantly used by people, and some of them are excreted unaltered or as metabolites through urine, with the sewage being the most important source to their release to the environment. These compounds are in almost all types of water (wastewater, surface water, groundwater, etc.) at concentrations ranging from ng/L to µg/L. The isolation and concentration of the PPCPs from water achieves the appropriate sensitivity. This step is mostly based on solid-phase extraction (SPE) but also includes other approaches (dispersive liquid-liquid microextraction (DLLME), buckypaper, SPE using multicartridges, etc.). In this review article, we aim to discuss the procedures employed to extract PPCPs from any type of water sample prior to their determination via an instrumental analytical technique. Furthermore, we put forward not only the merits of the different methods available but also a number of inconsistencies, divergences, weaknesses and disadvantages of the procedures found in literature, as well as the systems proposed to overcome them and to improve the methodology. Environmental applications of the developed techniques are also discussed. The pressing need for new analytical innovations, emerging trends and future prospects was also considered.