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The Drug Developments of Hydrogen Sulfide on Cardiovascular Disease
Ya-Dan Wen1,2,3, Hong Wang3,4, Yi-Zhun Zhu3,5
1Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.
Abstract:
The recognition of hydrogen sulfide (H2S) has been evolved from a toxic gas to a physiological mediator, exhibiting properties similar to NO and CO. On the one hand, H2S is produced from L-cysteine by enzymes of cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3MST) in combination with aspartate aminotransferase (AAT) (also called as cysteine aminotransferase, CAT); on the other hand, H2S is produced from D-cysteine by enzymes of D-amino acid oxidase (DAO). Besides sulfide salt, several sulfide-releasing compounds have been synthesized, including organosulfur compounds, Lawesson's reagent and analogs, and plant-derived natural products. Based on garlic extractions, we synthesized S-propargyl-L-cysteine (SPRC) and its analogs to contribute our endeavors on drug development of sulfide-containing compounds. A multitude of evidences has presented H2S is widely involved in the roles of physiological and pathological process, including hypertension, atherosclerosis, angiogenesis, and myocardial infarcts. This review summarizes current sulfide compounds, available H2S measurements, and potential molecular mechanisms involved in cardioprotections to help researchers develop further applications and therapeutically drugs.
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