Department of Chemistry, Wake Forest University, Winston-Salem, North Carolina 27109, USA.
Chemistry. 2012 Oct 8;18(41):12926-34. doi: 10.1002/chem.201202050. Epub 2012 Sep 17.
Nonclassical platinum-based antitumor agents have shown enormous potential in the treatment of chemoresistant cancers. The design of these agents is based on the hypothesis that platinum-containing pharmacophores that react with nuclear DNA in cancer cells radically differently than the clinical agent cisplatin will produce a unique spectrum of biological activity. One such class of molecules are platinum-acridine hybrid agents derived from the prototypical complex PtCl(en)(ACRAMTU)(2), en = ethane-1,2-diamine, ACRAMTU = 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea ("PT-ACRAMTU"). This article summarizes milestones in the development of these agents and reviews critical key concepts that have guided their design and that of related compounds.
非经典铂类抗肿瘤药物在治疗耐药性癌症方面显示出巨大的潜力。这些药物的设计基于这样一种假设，即与核 DNA 反应的含铂药效团与临床药物顺铂在癌细胞中的反应方式截然不同，将产生独特的生物学活性谱。一类这样的分子是源自原型配合物 PtCl(en)(ACRAMTU)(2) 的铂吖啶杂化剂，其中 en = 乙二胺，ACRAMTU = 1-[2-(吖啶-9-基氨基)乙基]-1,3-二甲基硫脲（“PT-ACRAMTU”）。本文总结了这些药物的发展里程碑，并回顾了指导其设计和相关化合物设计的关键关键概念。
