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1,2,4-Thiadiazolidin-3,5-diones as novel hydrogen sulfide donors
European Journal of Medicinal Chemistry ( IF 6.7 ) Pub Date : 2017-11-11 , DOI: 10.1016/j.ejmech.2017.10.068
Beatrice Severino , Angela Corvino , Ferdinando Fiorino , Paolo Luciano , Francesco Frecentese , Elisa Magli , Irene Saccone , Paola Di Vaio , Valentina Citi , Vincenzo Calderone , Luigi Servillo , Rosario Casale , Giuseppe Cirino , Valentina Vellecco , Mariarosaria Bucci , Elisa Perissutti , Vincenzo Santagada , Giuseppe Caliendo

Hydrogen sulfide (H2S) is an endogenous modulator that plays significant physio-pathological roles in several biological systems. In this research field there is a large interest in developing selective CBS and CSE inhibitors and H2S releasing moieties, that could be either used as therapeutic agents or linked to known drugs. One of the major problem is the limited availability of chemicals that ensure a controlled release of H2S in vitro as well in vivo. Aiming to obtain novel H2S donors, whose release properties could be appropriately modulated, we have synthesized a series of 1,2,4-thiadiazolidine-3,5-diones (THIA 1–10) as innovative donors that could release H2S in controlled manner. All the synthesized compounds were evaluated for their H2S releasing properties by an amperometric approach and for their vasorelaxant ability on aorta rings. In order to rationalize the obtained results, a detailed study on the release mechanism has been performed using the most efficient H2S donor, THIA 3 (Cmax 65.4 μM and EC50 1.7 μM).



中文翻译:

1,2,4-噻二唑烷-3,5-二酮类化合物作为新型硫化氢供体

硫化氢(H 2 S)是一种内源性调节剂,在几种生物系统中起着重要的生理病理作用。在该研究领域中,人们对开发选择性的CBS和CSE抑制剂以及H 2 S释放部分非常感兴趣,它们既可以用作治疗剂,也可以与已知药物连接。主要问题之一是确保体外和体内H 2 S受控释放的化学药品的供应有限。为了获得可以适当调节释放特性的新型H 2 S供体,我们合成了一系列1,2,4-噻二唑烷-3,5-二酮(THIA 1-10)作为可以释放H 2的创新性供体。S以受控方式。通过电流分析法评估所有合成的化合物的H 2 S释放特性,以及对主动脉环的血管舒张能力。为了使获得的结果合理化,已使用最有效的H 2 S供体THIA 3(C max 65.4μM和EC 50 1.7μM)对释放机理进行了详细研究。

更新日期:2017-11-11
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