Hanif Muhammad, Babak Maria V, Hartinger Christian G
School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
Drug Discov Today. 2014 Oct;19(10):1640-8. doi: 10.1016/j.drudis.2014.06.016. Epub 2014 Jun 21.
Platinum compounds are one of the pillars of modern cancer chemotherapy. The apparent disadvantages of existing chemotherapeutics have led to the development of novel anticancer agents with alternative modes of action. Many complexes of the heavy metal osmium (Os) are potent growth inhibitors of human cancer cells and are active in vivo, often superior or comparable to cisplatin, as the benchmark metal-based anticancer agent, or clinically tested ruthenium (Ru) drug candidates. Depending on the choice of ligand system, osmium compounds exhibit diverse modes of action, including redox activation, DNA targeting or inhibition of protein kinases. In this review, we highlight recent advances in the development of osmium anticancer drug candidates and discuss their cellular mechanisms of action.
铂类化合物是现代癌症化疗的支柱之一。现有化疗药物明显的缺点促使人们开发具有不同作用方式的新型抗癌药物。重金属锇(Os)的许多配合物是人类癌细胞的有效生长抑制剂,并且在体内具有活性,通常优于作为基准金属基抗癌药物的顺铂或与之相当,或者优于经过临床测试的钌(Ru)候选药物。根据配体系统的选择,锇化合物表现出多种作用方式,包括氧化还原激活、靶向DNA或抑制蛋白激酶。在本综述中,我们重点介绍了锇抗癌候选药物开发的最新进展,并讨论了它们的细胞作用机制。