Journal of Advanced Research ( IF 11.4 ) Pub Date : 2021-05-20 , DOI: 10.1016/j.jare.2021.05.008 Angela Corvino 1 , Valentina Citi 2 , Ferdinando Fiorino 1 , Francesco Frecentese 1 , Elisa Magli 1 , Elisa Perissutti 1 , Vincenzo Santagada 1 , Vincenzo Calderone 2 , Alma Martelli 2 , Era Gorica 2 , Simone Brogi 2 , Flavia Faganello Colombo 3 , Caroline Nunes Capello 3 , Heloisa Helena Araujo Ferreira 4 , Maria Grazia Rimoli 1 , Federica Sodano 5 , Barbara Rolando 5 , Francesca Pavese 6 , Antonio Petti 6 , Marcelo Nicolás Muscará 4 , Giuseppe Caliendo 1 , Beatrice Severino 1
|
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.
中文翻译：
H2S 贡献皮质类固醇：哮喘小鼠模型的设计、合成和生物学评价
介绍
硫化氢 (H 2 S) 是呼吸系统中基本的生物内源性气体介质。它调节关键的病理生理过程，如氧化应激、肺循环、气道张力和炎症。
目标
我们在此描述了通过几种皮质类固醇与不同的硫化氢释放部分的缩合获得的分子杂化物的设计和合成。
方法
所有分子都具有通过电流分析法和使用荧光探针释放 H 2 S 的能力。新合成的杂化分子的化学稳定性已在不同 pH 值和人血清中进行了研究。
结果
选择泼尼松-TBZ 杂化物（化合物7 ）进行进一步评估。体外和体内研究获得的结果清楚地显示了有利于释放的 H 2 S抗炎特性的证据。
结论
对气道重塑的保护作用使得混合泼尼松-TBZ（化合物7）成为减少过敏性哮喘症状和恶化的有前途的治疗选择。
京公网安备 11010802027423号