Abstract
Polybrominated diphenyl ethers (PBDEs) are a group of molecules with an ambiguous background in literature. PBDEs were first isolated from marine sponges of Dysidea 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.
Highlights
The search for new bioactive substances, which can overcome intrinsic or acquired resistance, are core topics of pharmaceutical research
This article summarizes the two research aspects, (i) the marine compound chemistry research dealing with naturally produced Polybrominated diphenyl ethers (PBDEs) and (ii) the environmental toxicology research dealing with synthetically-produced brominated flameretardant PBDEs
Natural products offer a high degree of structural diversity, including highly complex carbon scaffolds, along with advantageous pharmacokinetic and pharmacodynamic properties compared to synthetic substances due to their formation and evolution in biological systems [3]
Summary
The search for new bioactive substances, which can overcome intrinsic or acquired resistance, are core topics of pharmaceutical research. Ecological niches under high evolutionary pressure often yield bioactive compounds with high antibacterial or antineoplastic capacity (e.g., coral reefs). These compounds and their analogs from stress-exposed marine organisms or fungal endophytes could serve as a pool for new, potentially active compounds to elucidate the modes of action and overcome resistance at the molecular level. Natural products offer a high degree of structural diversity, including highly complex carbon scaffolds, along with advantageous pharmacokinetic and pharmacodynamic properties compared to synthetic substances due to their formation and evolution in biological systems [3]
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