Zhang Christiana Xin, Lippard Stephen J
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 01239, USA.
Curr Opin Chem Biol. 2003 Aug;7(4):481-9. doi: 10.1016/s1367-5931(03)00081-4.
The many activities of metal ions in biology have stimulated the development of metal-based therapeutics. Cisplatin, as one of the leading metal-based drugs, is widely used in treatment of cancer, being especially effective against genitourinary tumors such as testicular. Significant side effects and drug resistance, however, have limited its clinical applications. Biological carriers conjugated to cisplatin analogs have improved specificity for tumor tissue, thereby reducing side effects and drug resistance. Platinum complexes with distinctively different DNA binding modes from that of cisplatin also exhibit promising pharmacological properties. Ruthenium and gold complexes with antitumor activity have also evolved. Other metal-based chemotherapeutic compounds have been investigated for potential medicinal applications, including superoxide dismutase mimics and metal-based NO donors/scavengers. These compounds have the potential to modulate the biological properties of superoxide anion and nitric oxide.
金属离子在生物学中的多种活性推动了金属基疗法的发展。顺铂作为主要的金属基药物之一,被广泛用于癌症治疗,尤其对睾丸等泌尿生殖系统肿瘤疗效显著。然而,其严重的副作用和耐药性限制了它的临床应用。与顺铂类似物偶联的生物载体提高了对肿瘤组织的特异性,从而减少了副作用和耐药性。与顺铂具有明显不同DNA结合模式的铂配合物也表现出有前景的药理特性。具有抗肿瘤活性的钌和金配合物也得到了发展。其他金属基化疗化合物也已被研究用于潜在的医学应用,包括超氧化物歧化酶模拟物和金属基一氧化氮供体/清除剂。这些化合物有调节超氧阴离子和一氧化氮生物学特性的潜力。