Chin. J. Org. Chem. ›› 2019, Vol. 39 ›› Issue (5): 1503-1508.DOI: 10.6023/cjoc201811031 Previous Articles     Next Articles



胡曰富a, 崔桂玲a, 黄文才b, 杨黎c, 齐庆蓉a   

  1. a 四川大学华西药学院 靶向药物与释药系统教育部重点实验室 四川省植物来源药物工程实验室 四川省药物精密工业技术研究中心 成都 610041;
    b 四川大学化学工程学院 成都 610065;
    c 四川大学华西医院肿瘤中心 成都 610041
  • 收稿日期:2018-11-26 修回日期:2018-12-26 发布日期:2019-01-10
  • 通讯作者: 杨黎, 齐庆蓉;
  • 基金资助:


Synthesis, Structural Characterization and Stability Evaluation of Metformin Hydrosulfide

Hu Yuefua, Cui Guilinga, Huang Wencaib, Yang Lic, Qi Qingronga   

  1. a Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center of Drug Precision Industrial Technology for Small Molecule Drugs, West China School of Pharmacy, Sichuan University, Chengdu 610041;
    b School of Chemical Engineering, Sichuan University, Chengdu 610065;
    c Cancer Center, West China Hospital, Sichuan University, Chengdu 610041
  • Received:2018-11-26 Revised:2018-12-26 Published:2019-01-10
  • Contact: 10.6023/cjoc201811031;
  • Supported by:

    Project supported by the Construction of a Comprehensive Platform for the Innovation of Cardio-cerebrovascular Drugs in Shijiazhuang Pharmaceutical Group Company Limited (No. 2013ZX09402103-1).

Hydrogen sulfide (H2S), the third gas signal molecule in mammals is studied more and more deeply, and great progress has been made on organic small molecule hydrogen sulfide donors. However, no hydrogen sulfide donor has been marketed as a drug yet. Metformin is a first-line drug for the treatment of diabetes. And some other biological activities such as anti-obesity, anticancer, and anti-aging have been disclosed in recent years. H2S donor has also shown promising prospect in antitumor, cardiovascular protection, anti-inflammation, ion channel regulation and anti-oxidation activities. In view of the potential of hydrogen sulfide and metformin for treatment of diseases, a novel hydrogen sulfide donor, metformin hydrosulfide, was thus designed. Till now, there is no report of this type of hydrogen sulfide donor. In our work, metformin hydrochloride was first basified to obtain metformin, followed by reaction with hydrogen sulfide to afford metformin hydrosulfide. The structure was fully characterized by 1H NMR, 13C NMR, elemental analysis and X-ray crystal. The content of hydrogen sulfide was determined by iodometry method, lead acetate test and methylene blue spectrophotometric method to be more than 96.00%. The metformin level was determined by high-pressure liquid chromatography (HPLC) to be more than 98.50%. The stability of metformin hydrosulfide was evaluated by iodometry method in solution and solid, respectively. The results indicate that metformin hydrosulfide is a promising new type of hydrogen sulfide donor which deserves further research and development.

Key words: metformin hydrosulfide, hydrogen sulfide donor, hydrogen sulfide-based therapeutics