Details

Autor(en) / Beteiligte

• Milani, Gualtiero
• Budriesi, Roberta
• Tavazzani, Elisa
• Cavalluzzi, Maria Maddalena
• Mattioli, Laura Beatrice
• Miniero, Daniela Valeria
• Delre, Pietro
• Belviso, Benny Danilo
• Denegri, Marco
• Cuocci, Corrado
• Rotondo, Natalie Paola
• De Palma, Annalisa
• Gualdani, Roberta
• Caliandro, Rocco
• Mangiatordi, Giuseppe Felice
• Kumawat, Amit
• Camilloni, Carlo
• Priori, Silvia
• Lentini, Giovanni

Titel

hERG stereoselective modulation by mexiletine-derived ureas: Molecular docking study, synthesis, and biological evaluation

Ist Teil von

• Archiv der Pharmazie (Weinheim), 2023-10, Vol.356 (10), p.e2300116-e2300116

Ort / Verlag

Germany: Wiley Subscription Services, Inc

Erscheinungsjahr

2023

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Long QT syndrome (LQTS) is a disorder of cardiac electrophysiology resulting in life-threatening arrhythmias; nowadays, only a few drugs are available for the management of LQTS. Focusing our attention on LQT2, one of the most common subtypes of LQTS caused by mutations in the human ether-à-go-go-related gene (hERG), in the present work, the stereoselectivity of the recently discovered mexiletine-derived urea 8 was investigated on the hERG potassium channel. According to preliminary in silico predictions, in vitro studies revealed a stereoselective behavior, with the meso form showing the greatest hERG opening activity. In addition, functional studies on guinea pig isolated left atria, aorta, and ileum demonstrated that 8 does not present any cardiac or intestinal liability in our ex vivo studies. Due to its overall profile, (R,S)-8 paves the way for the design and development of a new series of compounds potentially useful in the treatment of both congenital and drug-induced forms of LQTS.