Acta Chimica Sinica ›› 2004, Vol. 62 ›› Issue (14): 1299-1304. Previous Articles     Next Articles

抗癌药物阿克拉霉素A的氧化还原代谢机理研究

程圭芳, 丁敏, 赵洁, 何品刚, 方禹之   

  1. 华东师范大学化学系, 上海, 200062
  • 投稿日期:2003-10-27 修回日期:2004-03-29 发布日期:2014-02-17
  • 通讯作者: 方禹之,E-mial:yuzhi@online.sh.cn E-mail:yuzhi@online.sh.cn
  • 基金资助:
    国家自然科学基金(No.2985008)资助项目.

Study on the Redox Metabolism Mechanism of Aclacinomycin-A

CHENG Gui-Fang, DING Min, ZHAO Jie, HE Pin-Gang, FANG Yu-Zhi   

  1. Department of Chemistry, East China Normal University, Shanghai 200062
  • Received:2003-10-27 Revised:2004-03-29 Published:2014-02-17

Normal University, Shanghai 200062) Aclacinomycin, with high eutherapeuticity and low toxicity, is a new compound of anthacyclines, when the application of other anthracycline drugs in therapeutics is heavily restricted by their high toxicity.Up to now, it is still a question of antitumor action of ACM and its low toxicity.Antitumor activity, cardiotoxicity and cytotoxicity of these kinds of medicine are closely related to their redox behavior in vivo.In this work, an investigation of the redox mechanism of ACM-A in simulated metabolic process was made and a possible reduction mechanism of ACM-A was proposed: ACM-A is able to get two electrons becoming hydroaclarimycinone-A, then partly goes on a deaglycone to form 7-deoxyaclarimycinone in neutral and alkaline media.Two of 7-deoxyaclarimycinone can associate.As no semiquinone free radicals are produced in reduction and no free radical chain reaction exists to cause the damage of mitochondria DNA in heart and other cells, with low cardiotoxicity and cytotoxicity, ACM-A has wilder application in clinical.Another result obtained in this work is that the reduction of anthracycline drug and side effect in therapy was correlated to its aglycone structure.The results obtained offered new method for medical design and selection.

Key words: aclacinomycin, metabolic mechanism, anthracycline, spectroelectrochemistry