Carbazole and simplified derivatives: Novel tools toward β-adrenergic receptors targeting

b-Adrenergic receptors (b-ARs) are G protein-coupled receptors involved in important physiological and pathological processes related to blood pressure and cardiac activity. The inhibition of cardiac b1-ARs could be beneficial in myocardial hypertrophy, ischemia and failure. Several carbazole-based compounds have been described as promising b-blockers. Herein, we investigate the capability of a carbazole derivative and three simplified indole analogs to interact with the active binding site of b1-AR by molecular docking studies. In the light of the obtained results, our compounds were tested by biological assays in H9c2 cardiomyocytes exposed to isoproterenol (ISO) to confirm their potential as b1-blockers agents, and two of them (8 and 10) showed interesting and promising properties. In particular, these compounds were effective against ISO-dependent in vitro cardiac hypertrophy, even at concentrations lower than the known b-AR antagonist propranolol. Overall, the data suggest that the indole derivatives 8 and 10 could act as potent b1-blockers and, active at low doses, could elicit limited side effects