title: Aquaporin inhibition by gold(III) compounds: new insights.
abstract: Aquaporins (AQPs) are membrane water/glycerol channels with essential roles in biological systems, as well as being promising targets for therapy and imaging. Using a stopped-flow method, a series of gold(III), platinum(II) and copper(II) complexes bearing nitrogen donor ligands, such as 1,10-phenatroline, 2,2'-bipyridine, 4,4'-dimethyl-2,2'-bipyridine, 4,4'-diamino-2,2'-bipyridine and 2,2';6',2"-terpyridine, were evaluated in human red blood cells expressing AQP1 and AQP3, responsible for water and glycerol movement, respectively. The results showed that the gold(III) complexes selectively modulate AQP3 over AQP1. Molecular modeling and density functional theory (DFT) calculations were subsequently performed to rationalize the observations and to investigate the possible molecular mechanism through which these gold compounds act on their putative target (AQP3). In the absence of any crystallographic data, a previously reported homology model was used for this purpose. Combined, the findings of this study show that potent and selective modulation of these solute channels is possible, however further investigation is required into the selectivity of this class of agents against all AQP isoforms and their potential therapeutic uses.
authors: Research Institute for Medicines & Pharmaceutical Sciences (iMed.UL), Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
authors: Ana Paula
authors: AP
authors: Martins
authors: Antonella
authors: A
authors: Ciancetta
authors: Andreia
authors: A
authors: de Almeida
authors: Alessandro
authors: A
authors: Marrone
authors: Nazzareno
authors: N
authors: Re
authors: Graça
authors: G
authors: Soveral
authors: Angela
authors: A
authors: Casini
mesh_terms: D020346:Aquaporins / Q000037:antagonists & inhibitors*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D050607:Organogold Compounds / Q000737:chemistry / Q000494:pharmacology*; D011789:Quantum Theory; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D020346:Aquaporins; D050607:Organogold Compounds