Fudan University, Shanghai 200032, People's Republic of China.
Expert Rev Clin Pharmacol. 2011 Jan;4(1):123-33. doi: 10.1586/ecp.10.129.
Hydrogen sulfide, once considered as toxic gas, is now recognized as an important biological mediator. The deficiency of hydrogen sulfide could lead to various pathological changes, such as arterial and pulmonary hypertension, Alzheimer's disease, gastric mucosal injury and liver cirrhosis. However, excessive production of hydrogen sulfide, by using inorganic hydrogen sulfide donors such as NaHS, may contribute to the pathogenesis of inflammatory diseases, septic shock, cerebral stroke and mental retardation in patients with Down syndrome. Therefore, an increasing interest in organic molecules that are capable of regulating the formation of hydrogen sulfide has extended in recent years. Allium vegetables are one natural source of organic sulfur-containing compounds and have been widely investigated regarding their therapeutic applications, and it has been proven that the ingredients of garlic, such as diallyl disulfide, diallyl trisulfide and S-ally cysteine act as hydrogen sulfide donors or mediators in pharmaceutical studies. In addition, S-propargyl cysteine (ZYZ-802) and S-propyl cysteine, two synthetic cysteine analogs, have been examined and could be used to treat ischemic heart disease via modulation of the hydrogen sulfide pathway. In addition, drugs containing hydrogen sulfide-releasing moieties have been synthesized and widely reported in recent years, such as S-nonsteroidal anti-inflammatory drugs and the derivative of Lawesson's reagents, which exhibit varied biological effects in experiments. As cystathionine β-synthase and cystathionine γ-lyase are the enzymes that are able to catalyze the production of endogenous hydrogen sulfide from cysteine, their inhibitors, such as dl-propylargylglycine and β-cyanoalanine, have been frequently used in studies on the biological mechanism of hydrogen sulfide. All these hydrogen sulfide donors, mediators and inhibitors have provided useful tools in the research of a variety of biological effects and are promising drug candidates of hydrogen sulfide.
硫化氢曾被认为是一种有毒气体，现在被认为是一种重要的生物调节剂。硫化氢的缺乏可导致各种病理变化，如动脉和肺动脉高压、阿尔茨海默病、胃黏膜损伤和肝硬化。然而，使用无机硫化氢供体如 NaHS 过度产生硫化氢，可能导致炎性疾病、脓毒性休克、脑卒中和唐氏综合征患者智力迟钝的发病机制。因此，近年来，人们对能够调节硫化氢形成的有机分子越来越感兴趣。葱属蔬菜是有机含硫化合物的天然来源之一，其治疗应用已得到广泛研究，已证明大蒜的成分，如二烯丙基二硫化物、二烯丙基三硫化物和 S-烯丙基半胱氨酸，在药物研究中作为硫化氢供体或调节剂。此外，两种合成半胱氨酸类似物 S-炔丙基半胱氨酸 (ZYZ-802) 和 S-丙基半胱氨酸已被研究，可通过调节硫化氢途径用于治疗缺血性心脏病。此外，近年来合成并广泛报道了含有硫化氢释放部分的药物，如 S-非甾体抗炎药和劳森试剂的衍生物，它们在实验中表现出不同的生物学效应。由于胱硫醚β-合酶和胱硫醚γ-裂解酶是能够从半胱氨酸催化内源性硫化氢产生的酶，它们的抑制剂，如 dl-丙基精氨酸甘氨酸和β-氰基丙氨酸，已被频繁用于研究硫化氢的生物学机制。所有这些硫化氢供体、调节剂和抑制剂为研究各种生物学效应提供了有用的工具，是硫化氢的有前途的候选药物。
