Lu Xiaohua, Efferth Thomas
Department of Pharmaceutical Biology, Institute of Pharmacy and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany.
Department of Pharmaceutical Biology, Institute of Pharmacy and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany.
Semin Cancer Biol. 2021 Jan;68:291-312. doi: 10.1016/j.semcancer.2020.05.016. Epub 2020 May 30.
Cancer treatment represents an unmet challenge due to the development of drug resistance and severe side effects of chemotherapy. Artemisinin (ARS)-type compounds exhibit excellent antimalarial effects with few side effects and drug-resistance. ARS and its derivatives were also reported to act against various tumor types in vitro and in vivo, including acute leukemia. Therefore, ARS-type compounds may be exquisitely suitable for repurposing in leukemia treatment. To provide comprehensive clues of ARS and its derivatives for acute leukemia treatment, their molecular mechanisms are discussed in this review. Five monomeric molecules and 72 dimers, trimers and hybrids based on the ARS scaffold have been described against acute leukemia. The modes of action involve anti-angiogenic, anti-metastatic and growth inhibitory effects. These properties make ARS-type compounds as potential candidates for the treatment of acute leukemia. Still, more potent and target-selective ARS-type compounds need to be developed.
由于耐药性的产生和化疗的严重副作用,癌症治疗面临着尚未解决的挑战。青蒿素(ARS)类化合物具有出色的抗疟效果,副作用少且不易产生耐药性。据报道,ARS及其衍生物在体外和体内对包括急性白血病在内的各种肿瘤类型都有作用。因此,ARS类化合物可能非常适合用于白血病治疗的药物重新利用。为了提供ARS及其衍生物用于急性白血病治疗的全面线索,本综述讨论了它们的分子机制。已经描述了基于ARS支架的5种单体分子以及72种二聚体、三聚体和杂化物对急性白血病的作用。其作用方式包括抗血管生成、抗转移和生长抑制作用。这些特性使ARS类化合物成为治疗急性白血病的潜在候选药物。不过,仍需要开发更有效且具有靶点选择性的ARS类化合物。