H2S donating corticosteroids: Design, synthesis and biological evaluation in a murine model of asthma

被引：20

作者：

Corvino, Angela ^{[1
]}

Citi, Valentina ^{[2
]}

Fiorino, Ferdinando ^{[1
]}

Frecentese, Francesco ^{[1
]}

Magli, Elisa ^{[1
]}

Perissutti, Elisa ^{[1
]}

Santagada, Vincenzo ^{[1
]}

Calderone, Vincenzo ^{[2
]}

Martelli, Alma ^{[2
]}

Gorica, Era ^{[2
]}

Brogi, Simone ^{[2
]}

Colombo, Flavia Faganello ^{[3
]}

Capello, Caroline Nunes ^{[3
]}

Araujo Ferreira, Heloisa Helena ^{[4
]}

Rimoli, Maria Grazia ^{[1
]}

Sodano, Federica ^{[5
]}

Rolando, Barbara ^{[5
]}

Pavese, Francesca ^{[6
]}

Petti, Antonio ^{[6
]}

Muscara, Marcelo Nicolas ^{[4
]}

Caliendo, Giuseppe ^{[1
]}

Severino, Beatrice ^{[1
]}

机构：

[1] Univ Naples Federico II, Sch Med, Dept Pharm, Via D Montesano 49, I-80131 Naples, Italy

[2] Univ Pisa, Dept Pharm, Via Bonanno 6, I-56126 Pisa, Italy

[3] Sao Leopoldo Mand Inst & Res Ctr, BR-13045755 Campinas, SP, Brazil

[4] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, BR-05508000 Sao Paulo, SP, Brazil

[5] Univ Torino, Dept Drug Sci & Technol, Via Pietro Giuria 9, I-10125 Turin, Italy

[6] Genetic SpA, Via Monica 26, I-2684083 Castel San Giorgio, SA, Italy

来源：

JOURNAL OF ADVANCED RESEARCH | 2022年 / 35卷

基金：

巴西圣保罗研究基金会;

关键词：

Hydrogen sulfide; H2S releasing compounds; Steroidal anti-inflammatory drugs; Hybrids; Asthma; Lung diseases; HYDROGEN-SULFIDE DONORS; GASOTRANSMITTER; ACTIVATION; RELEASE;

D O I：

10.1016/j.jare.2021.05.008

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Introduction: Hydrogen sulfide (H2S) 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 H2S 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 H2S. 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. (C) 2021 The Authors. Published by Elsevier B.V. on behalf of Cairo University.

引用

页码：267 / 277

页数：11

共 51 条

[1] Targeting cytokines to treat asthma and chronic obstructive pulmonary disease [J].