Giralt Ernest, Lo Re Daniele
Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, C/Baldiri Reixac 10, Barcelona E-08028, Spain.
Department of Organic Chemistry, University of Barcelona, Marti i Franques 1-11, Barcelona E-08028, Spain.
Molecules. 2017 Feb 9;22(2):198. doi: 10.3390/molecules22020198.
Tumor metastasis is a complex process in which cells detach from the primary tumor and colonize a distant organ. Metastasis is also the main process responsible for cancer-related death. Despite the enormous efforts made to unravel the metastatic process, there is no effective therapy, and patients with metastatic tumors have poor prognosis. In this regard, there is an urgent need for new therapeutic tools for the treatment of this disease. Small molecules with the capacity to reduce cell migration could be used to treat metastasis. Migrastatin-core analogs are naturally inspired macrocycles that inhibit pathological cell migration and are able to reduce metastasis in animal models. Migrastatin analogs can be synthesized from a common advanced intermediate. Herein we present a review of the synthetic approaches that can be used to prepare this key intermediate, together with a review of the biological activity of migrastatin-core analogs and current hypotheses concerning their mechanism of action.
肿瘤转移是一个复杂的过程,在此过程中细胞从原发性肿瘤脱离并在远处器官定植。转移也是导致癌症相关死亡的主要过程。尽管人们为揭示转移过程付出了巨大努力,但仍没有有效的治疗方法,转移性肿瘤患者的预后很差。在这方面,迫切需要用于治疗这种疾病的新治疗工具。具有降低细胞迁移能力的小分子可用于治疗转移。迁移他汀核心类似物是受自然启发的大环化合物,可抑制病理性细胞迁移,并能够在动物模型中减少转移。迁移他汀类似物可由一种常见的高级中间体合成。本文综述了可用于制备这种关键中间体的合成方法,以及迁移他汀核心类似物的生物活性和有关其作用机制的当前假说。