Cation, anion and ion-pair complexes with a G-3 poly(ethylene imine) dendrimer in aqueous solution

The G-3 poly(ethylene imine) ligand L2 shows a multifaceted coordination ability, being able to bind metal cations, anions and ion-pairs. The equilibrium constants for the formation of metal (Cu2+, Zn2+), anion (SO42−) and ion-pair (Cu2+/SO42−) complexes were determined in 0.1 M Me4NCl aqueous solution at 298.1 ± 0.1 K by means of potentiometric titrations. Thanks to its dendrimeric nature, L2 can form highly nucleated metal complexes, such as Cu5L210+ and Zn4L28+, in successive and well-defined complexation steps. Protonated forms of L2 give rise to relatively weak anion complexes with SO42−, but the addition of Cu2+ significantly enhances the binding ability of the ligand toward this anion below pH 9. In more alkaline solutions, an opposite trend is observed. The coordination properties of L2 are discussed with the support of modelling calculations. According to results, L2 is a promising molecule for the preparation of solid supported materials for the recovery of cations and anions from aqueous media and/or for applications in heterogeneous catalysis

Calixarenes Incorporating Sulfonamide Moieties: Versatile Ligands for Carbonic Anhydrases Inhibition

Carbonic anhydrases (CAs) continue to represent a relevant pharmaceutical target. The need of selective inhibitors and the involvement of these metalloenzymes in many multifaceted diseases boost the search for new ligands able to distinguish among the different CA isoforms, and for multifunctional systems simultaneously able to inhibit CAs and to interfere with other pathological events by interacting with additional targets. In this work, we successfully explored the possibility of preparing new CAs ligands by combining calixarenes with benzensulfonamide units. Inhibition tests towards three human CA isoforms evidenced, for some of the ligands, Ki values in the nanomolar range and promising selectivity. X-ray and molecular modeling studies provided information on the mode of binding of these calixarene derivatives. Thanks to the encouraging results and the structural features typical of the calixarene scaffold, it is then possible to plan for the future the design of multifunctional inhibitors for this class of widely spread enzymes

Design and synthesis of sulfonamides incorporating a biotin moiety: Carbonic anhydrase inhibitory effects, antiproliferative activity and molecular modeling studies

: Sulfonamides constitute an important class of classical carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. Herein we have accomplished the conjugation of biotin with an ample number of sulfonamide motifs with the aim of testing them in vitro as inhibitors of the human carbonic anhydrase (hCA) isoforms I and II (cytosolic isozymes), as well as hCA IX and XII (transmembrane, tumor-associated enzymes). Most of these newly synthesized compounds exhibited interesting inhibition profiles, with activities in the nanomolar range. The presence of a 4-F-C6H4 moiety, also found in SLC-0111, afforded an excellent selectivity towards the tumor-associated hypoxia-induced hCA isoform XII with an inhibition constant (KI) of 4.5 nM. The 2-naphthyl derivative was the most potent inhibitor against hCA IX (KI = 6.2 nM), 4-fold stronger than AAZ (KI = 25 nM) with very good selectivity. Some compounds were chosen for antiproliferative activity testing against a panel of 3 human tumor cell lines, one compound showing anti-proliferative activity on glioblastoma, triple-negative breast cancer, and pancreatic carcinoma cell lines