Department of Oncology and Hematology, Zibo 148 Hospital, Zibo, China.
Department of General Surgery, People's Hospital of Zhoucun District, Zibo, China.
Arch Pharm (Weinheim). 2024 Mar;357(3):e2300641. doi: 10.1002/ardp.202300641. Epub 2023 Dec 18.
Breast cancer, as one of the most common invasive malignancies and the leading cause of cancer-related deaths in women globally, poses a significant challenge in the world health system. Substantial advances in diagnosis and treatment have significantly improved the survival rate of breast cancer patients, but the number of incidences and deaths of breast cancer are projected to increase by 40% and 50%, respectively, by 2040. Chemotherapy is one of the principal treatments for breast cancer therapy, but multidrug resistance and severe side effects remain the major obstacles to the success of treatment. Hence, there is a vital need to develop novel chemotherapeutic agents to combat this deadly disease. 1,2,3-Triazole, which can be effectively constructed by click chemistry, not only can serve as a linker to connect different anti-breast cancer pharmacophores but also is a valuable pharmacophore with anti-breast cancer potential and favorable properties such as hydrogen bonding, moderate dipole moment, and enhanced water solubility. Particularly, 1,2,3-triazole-containing hybrids have demonstrated promising in vitro and in vivo anti-breast cancer potential against both drug-sensitive and drug-resistant forms and possessed excellent selectivity by targeting different biological pathways associated with breast cancer, representing privileged scaffolds for the discovery of novel anti-breast cancer candidates. This review concentrates on the latest advancements of 1,2,3-triazole-containing hybrids with anti-breast cancer potential, including work published between 2020 and the present. The structure-activity relationships (SARs) and mechanisms of action are also reviewed to shed light on the development of more effective and multitargeted candidates.
乳腺癌是全球范围内最常见的侵袭性恶性肿瘤之一，也是导致女性癌症相关死亡的主要原因，对全球卫生系统构成了重大挑战。在诊断和治疗方面的重大进展显著提高了乳腺癌患者的生存率，但预计到 2040 年，乳腺癌的发病率和死亡率将分别增加 40%和 50%。化疗是乳腺癌治疗的主要方法之一，但多药耐药和严重的副作用仍然是治疗成功的主要障碍。因此，迫切需要开发新的化疗药物来对抗这种致命疾病。1,2,3-三唑可以通过点击化学有效地构建，不仅可以作为连接不同抗乳腺癌药效团的连接子，而且是一种具有抗乳腺癌潜力和良好性质的药效团，如氢键、适度的偶极矩和增强的水溶性。特别是，含有 1,2,3-三唑的杂合化合物在体外和体内对敏感和耐药形式的乳腺癌均显示出有希望的抗乳腺癌潜力，并通过靶向与乳腺癌相关的不同生物途径具有优异的选择性，代表了发现新型抗乳腺癌候选药物的优势骨架。本综述重点介绍了具有抗乳腺癌潜力的含 1,2,3-三唑的杂合化合物的最新进展，包括 2020 年至今发表的工作。还综述了构效关系 (SAR) 和作用机制，以阐明开发更有效和多靶点候选药物的方法。
