Institute for Molecular Medicine I, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Universitätsstraße 1, 40225 Düsseldorf, Germany.
Institute for Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf, Universitätsstraße 1, 40225 Düsseldorf, Germany.
Molecules. 2021 Feb 13;26(4):995. doi: 10.3390/molecules26040995.
Polybrominated diphenyl ethers (PBDEs) are a group of molecules with an ambiguous background in literature. PBDEs were first isolated from marine sponges of species in 1981 and have been under continuous research to the present day. This article summarizes the two research aspects, (i) the marine compound chemistry research dealing with naturally produced PBDEs and (ii) the environmental toxicology research dealing with synthetically-produced brominated flame-retardant PBDEs. The different bioactivity patterns are set in relation to the structural similarities and dissimilarities between both groups. In addition, this article gives a first structure-activity relationship analysis comparing both groups of PBDEs. Moreover, we provide novel data of a promising anticancer therapeutic PBDE (i.e., 4,5,6-tribromo-2-(2',4'-dibromophenoxy)phenol; termed P01F08). It has been known since 1995 that P01F08 exhibits anticancer activity, but the detailed mechanism remains poorly understood. Only recently, Mayer and colleagues identified a therapeutic window for P01F08, specifically targeting primary malignant cells in a low µM range. To elucidate the mechanistic pathway of cell death induction, we verified and compared its cytotoxicity and apoptosis induction capacity in Ramos and Jurkat lymphoma cells. Moreover, using Jurkat cells overexpressing antiapoptotic Bcl-2, we were able to show that P01F08 induces apoptosis mainly through the intrinsic mitochondrial pathway.
多溴二苯醚 (PBDEs) 是一类文献背景尚不明确的分子。PBDEs 于 1981 年首次从 种海洋海绵中分离出来，此后一直持续研究至今。本文总结了两个研究方面，（i）涉及天然产生的 PBDEs 的海洋化合物化学研究，以及（ii）涉及合成产生的溴化阻燃剂 PBDEs 的环境毒理学研究。这两组 PBDEs 的不同生物活性模式与它们之间的结构相似性和差异性有关。此外，本文还对这两组 PBDEs 进行了首次的结构-活性关系分析。此外，我们提供了一种有前途的抗癌治疗性 PBDE（即 4,5,6-三溴-2-(2',4'-二溴苯氧基)苯酚；称为 P01F08）的新数据。自 1995 年以来，人们已经知道 P01F08 具有抗癌活性，但详细的机制仍知之甚少。直到最近，Mayer 及其同事才确定了 P01F08 的治疗窗，该治疗窗专门针对低 µM 范围内的原发性恶性细胞。为了阐明诱导细胞死亡的机制途径，我们在 Ramos 和 Jurkat 淋巴瘤细胞中验证和比较了其细胞毒性和凋亡诱导能力。此外，我们使用 Jurkat 细胞过表达抗凋亡的 Bcl-2，证明 P01F08 主要通过内在的线粒体途径诱导细胞凋亡。
