Department of Chemistry, Tsinghua University, Beijing, 100084, PR China.
Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, PR China.
Eur J Med Chem. 2019 Nov 1;181:111587. doi: 10.1016/j.ejmech.2019.111587. Epub 2019 Aug 5.
Cancer is the second leading cause of death worldwide, and it results in around 9 million deaths annually. The anticancer agents play an intriguing role in the treatment of cancers, while the severe anticancer scenario and the emergence of drug-resistant especially multidrug-resistant cancers create a huge demand for novel anticancer drugs with different mechanisms of action. The coumarin scaffold is ubiquitous in nature and is a highly privileged motif for the development of novel drugs due to its biodiversity and versatility. Coumarin derivatives can exert diverse antiproliferative mechanisms, and some of them such as Irosustat are under clinical trials for the treatment of various cancers, revealing their potential as putative anticancer drugs. Hybridization of coumarin moiety with other anticancer pharmacophores is a promising strategy to reduce side effects, overcome the drug resistance, and may provide valuable therapeutic intervention for the treatment of cancers. Thus, coumarin-containing hybrids occupy an important position in the development of novel anticancer agents. This review aims to summarize the recent advances made towards the development of coumarin-containing hybrids as potential anticancer agents, covering articles published between 2015 and 2019, and the structure-activity relationship together with mechanisms of action are also discussed.
癌症是全球第二大死亡原因，每年导致约 900 万人死亡。抗癌剂在癌症治疗中发挥着引人注目的作用，而严重的抗癌情况和耐药性（特别是多药耐药性）癌症的出现，对具有不同作用机制的新型抗癌药物产生了巨大需求。香豆素骨架在自然界中普遍存在，由于其生物多样性和多功能性，是开发新型药物的高度特权基序。香豆素衍生物可以发挥多种抗增殖作用机制，其中一些，如 Irosustat，正在进行各种癌症的临床试验，显示出它们作为潜在抗癌药物的潜力。香豆素部分与其他抗癌药效团的杂化是降低副作用、克服耐药性的一种有前途的策略，可能为癌症治疗提供有价值的治疗干预。因此，含香豆素的杂合物在新型抗癌药物的开发中占据重要地位。本综述旨在总结 2015 年至 2019 年期间发表的关于香豆素类化合物作为潜在抗癌剂的最新进展，并讨论其结构-活性关系和作用机制。
