title: The Pharmacological Effects of S-Propargyl-Cysteine, a Novel Endogenous H2S-Producing Compound.
abstract: S-propargyl-cysteine (SPRC), also named as ZYZ-802, is a structural analog of S-allylcysteine (SAC), the most abundant constituent of aged garlic extract. SPRC becomes a derivative of the amino acid cysteine, which contains sulfur atom, by changing allyl group in SAC to propargyl group in SPRC. Another analog of SPRC and SAC is S-propyl cysteine (SPC), which has propyl group instead in its cysteine structure. Drug formulation of SPRC has been investigated in the mixture of extenders, such as lactose, microcrystalline cellulose, and cross-linked povidone, showing good fluidity and scale-up production possibility. Controlled release formulation of SPRC (CR-SPRC) and leonurine-SPRC were invented and shown the decent pharmacological effects in heart failure and hypoxia injury, respectively. The pharmacological effects of SPRC have been shown that cardioprotection and proangiogenesis in several ischemic heart models, neuroprotection in Alzheimer's disease, proapoptosis in gastric cancer and anti-inflammation in acute pancreatitis. Moreover, CR-SPRC reduced infarct size and recovered partial cardiac function in heart failure rat model. Leonurine-SPRC protected hypoxic neonatal rat ventricular myocytes in much lower dose. Interestingly, since the propagyl group in SPRC has the stronger chemical bond in the cysteine structure than allyl group in SAC and propyl group in SPC, SPRC showed more extensive cardioprotection in ischemic rat hearts model compared to SAC and SPC. The mechanisms of pharmacological effects of SPRC have been unveiled that SPRC reduced Ca2+ accumulation, activated antioxidants, inhibited STAT3, decreased inflammatory cytokines, and elevated p53 and Bax. More pharmacological effects and mechanisms of SPRC will be discovered in atherosclerosis, hypertension, and other diseases.
authors.affiliation: Department of Pharmacology, Clinical Research Centre School of Medicine, National University of Singapore, Bldg MD11, Level 5, # 05-09, 10 Medical Drive, Singapore, 117597, Singapore, yadan.wen@gmail.com.
authors.forename: Ya-Dan
authors.initials: YD
authors.lastname: Wen
authors.forename: Yi-Zhun
authors.initials: YZ
authors.lastname: Zhu
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical; D003545:Cysteine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006333:Heart Failure / Q000188:drug therapy; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000188:drug therapy; D018919:Neovascularization, Physiologic / Q000187:drug effects
chemical_list: C556437:S-propargylcysteine; D003545:Cysteine; D006862:Hydrogen Sulfide