Severino Beatrice, Corvino Angela, Fiorino Ferdinando, Luciano Paolo, Frecentese Francesco, Magli Elisa, Saccone Irene, Di Vaio Paola, Citi Valentina, Calderone Vincenzo, Servillo Luigi, Casale Rosario, Cirino Giuseppe, Vellecco Valentina, Bucci Mariarosaria, Perissutti Elisa, Santagada Vincenzo, Caliendo Giuseppe
Department of Pharmacy, School of Medicine, University of Naples «Federico II», Via D. Montesano, 49, 80131 Napoli, Italy.
Department of Pharmacy, School of Medicine, University of Naples «Federico II», Via D. Montesano, 49, 80131 Napoli, Italy.
Eur J Med Chem. 2018 Jan 1;143:1677-1686. doi: 10.1016/j.ejmech.2017.10.068. Epub 2017 Nov 11.
Hydrogen sulfide (HS) 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 HS 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 HS in vitro as well in vivo. Aiming to obtain novel HS 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 HS in controlled manner. All the synthesized compounds were evaluated for their HS 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 HS donor, THIA 3 (C 65.4 μM and EC 1.7 μM).
硫化氢（HS）是一种内源性调节剂，在多个生物系统中发挥着重要的生理病理作用。在这个研究领域，人们对开发选择性胱硫醚β-合成酶（CBS）和胱硫醚γ-裂解酶（CSE）抑制剂以及HS释放基团有着浓厚的兴趣，这些物质既可以用作治疗剂，也可以与已知药物相连。主要问题之一是确保HS在体外和体内实现可控释放的化学物质供应有限。为了获得能够适当调节释放特性的新型HS供体，我们合成了一系列1,2,4-噻二唑烷-3,5-二酮（THIA 1-10）作为创新型供体，它们能够以可控方式释放HS。通过安培法评估了所有合成化合物的HS释放特性，并评估了它们对主动脉环的血管舒张能力。为了合理解释所得结果，使用最有效的HS供体THIA 3（C 65.4 μM和EC 1.7 μM）对释放机制进行了详细研究。
