Carbazole and Simplified Derivatives: Novel Tools toward β-Adrenergic Receptors Targeting

beta-Adrenergic receptors (beta-ARs) are G protein-coupled receptors involved in important physiological and pathological processes related to blood pressure and cardiac activity. The inhibition of cardiac beta 1-ARs could be beneficial in myocardial hypertrophy, ischemia and failure. Several carbazole-based compounds have been described as promising beta-blockers. Herein, we investigate the capability of a carbazole derivative and three simplified indole analogs to interact with the active binding site of beta 1-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 beta 1-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 beta-AR antagonist propranolol. Overall, the data suggest that the indole derivatives 8 and 10 could act as potent beta 1-blockers and, active at low doses, could elicit limited side effects.

Automated summary

The study demonstrates that indole derivatives 8 and 10 have potential as potent beta 1-blockers, effectively inhibiting cardiac hypertrophy even at lower concentrations and with limited side effects.