Copper in medicine: homeostasis, chelation therapy and antitumor drug design.
As one of the most important essential transition metals, copper is involved in a variety of biological processes such as embryo development, connective tissue formation, temperature control and nerve cell function. It is also related to severe diseases such as Wilson's and Menkes diseases and some neurological disorders. Novel components of copper homeostasis include copper-transporting P-type ATPases, Menkes and Wilson proteins, and copper chaperones in humans have been identified and characterized at the molecular level. These findings have paved the way towards better understanding of the role of copper deficiency or copper toxicity in physiological and pathological conditions. Therefore, organic compounds that can interfere with copper homeostasis may find therapeutic application in copper-dependent diseases. The antitumor activity of copper complexes was reported several decades ago, and many new complexes have demonstrated great antitumor potential. Copper complexes may have relatively lower side effects than platinum-based drugs, and are suggested to be able to overcome inherited or acquired resistance of cisplatin. In this overview, the most recent advances in copper homeostasis, copper-related chelation therapy and design of copper-based antitumor complexes will be summarized.
Wang
Tuo
T
State Key Laboratory of Coordination Chemistry, Nanjing University, Nanjing 210093, P.R. China. zguo@nju.edu.cn.
Guo
Zijian
Z
D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D002614:Chelating Agents / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D003300:Copper / Q000737:chemistry / Q000378:metabolism*; D015195:Drug Design; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy*; D009942:Organometallic Compounds / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D002614:Chelating Agents; D009942:Organometallic Compounds; D003300:Copper