H2S donating corticosteroids: Design, synthesis and biological evaluation in a murine model of asthma
Angela Corvino, Valentina Citi, Ferdinando Fiorino, Francesco Frecentese, Elisa Magli, Elisa Perissutti, Vincenzo Santagada, Vincenzo Calderone, Alma Martelli, Era Gorica, Simone Brogi, Flávia Faganello Colombo, C. Capello, Heloisa Helena Araujo Ferreira, Maria Grazia Rimoli, Federica Sodano, Barbara Rolando, Francesca Pavese, Antonio Petti, Marcelo N. Muscará, Giuseppe Caliendo, Beatrice Severino
Abstract
Introduction Hydrogen sulfide (H 2 S) is a fundamental biological endogenous gas-mediator in the respiratory system. It regulates pivotal patho-physiological processes such as oxidative stress, pulmonary circulation, airway tone and inflammation. Objectives We herein describe the design and synthesis of molecular hybrids obtained by the condensation of several corticosteroids with different hydrogen sulfide releasing moieties. Methods All the molecules are characterized for their ability to release H 2 S both via amperometric approach and using a fluorescent probe . The chemical stability of the newly synthesized hybrid molecules has been investigated at differing pH values and in human serum. Results Prednisone-TBZ hybrid (compound 7 ) was selected for further evaluations. The obtained results from the in vitro and in vivo studies clearly show evidence in favor of the anti-inflammatory properties of the released H 2 S. Conclusions The protective effect on airway remodeling makes the hybrid Prednisone-TBZ (compound 7 ) as a promising therapeutic option in reducing allergic asthma symptoms and exacerbations.