Department of Emergency, Zhuji Affiliated Hospital of Shaoxing University, Zhuji, China.
Department of Gynaecology, Traditional China Medical Hospital of Zhuji, Zhuji, China.
Curr Top Med Chem. 2021;21(19):1773-1786. doi: 10.2174/1568026621666210804115203.
Cancer, a complex disease which involves abnormalities of multiple cellular pathways, is one of the most serious threatens to human health across the world. Chemotherapy with a single agent or a combined regimen is a standardized strategy for the treatment of almost all human cancers, and the cure rate of cancer increases with the continuous discovery of anticancer agents and the optimization of chemotherapy options. However, drug resistance, especially multidrug resistance, remains an obstacle in the effective treatment of cancer. Hence, it is urgent to develop novel agents with potential activity against cancers, especially drug-resistant forms. Acridine, which bears three fused rings, could intercalate into DNA and interfere with metabolic processes. Recently, acridines have been found with anticancer activity in a variety of malignancies through suppressing cell proliferation, stimulating apoptosis, and inducing cell cycle arrest, retarding migration, invasion and metastasis. Thus, acridines are useful scaffolds for the discovery of novel drug candidates with potent anticancer activity. This review focused on the current scenario of acridine hybrids with potential activity against cancers reported from Jan, 2015 to Feb, 2021. The mechanisms of action, the criteria of compound design as well as structure-activity relationships were also summarized to pave the way for a further rational design of novel anticancer agents.
癌症是一种涉及多个细胞通路异常的复杂疾病，是全球范围内对人类健康最严重的威胁之一。单一药物或联合治疗方案的化疗是治疗几乎所有人类癌症的标准策略，随着抗癌药物的不断发现和化疗方案的优化，癌症的治愈率也在不断提高。然而，耐药性，特别是多药耐药性，仍然是癌症有效治疗的障碍。因此，迫切需要开发具有潜在抗癌活性的新型药物，特别是针对耐药形式的药物。吖啶具有三个稠合环，可以插入 DNA 并干扰代谢过程。最近，吖啶类化合物已被发现具有多种恶性肿瘤的抗癌活性，通过抑制细胞增殖、刺激细胞凋亡和诱导细胞周期停滞、抑制迁移、侵袭和转移。因此，吖啶类化合物是发现具有强大抗癌活性的新型候选药物的有用支架。本文综述了 2015 年 1 月至 2021 年 2 月间报道的具有潜在抗癌活性的吖啶类杂合化合物的最新研究进展。还总结了作用机制、化合物设计标准以及构效关系，为进一步合理设计新型抗癌药物铺平了道路。
