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Synthesis of novel purpurealidin analogs and evaluation of their effect on the cancerrelevant potassium channel KV10.1
Moreels, L.; Bhat, C.; Vorácová, M.; Peigneur, S.; Mäki-Lohiluoma, E.; Zahed, F.; Pardo, L.A.; Yli-Kauhaluoma, J.; Kiuru, P.; Tytgat, J. (2017). Synthesis of novel purpurealidin analogs and evaluation of their effect on the cancerrelevant potassium channel KV10.1. PLoS One 12(12): e0188811. https://hdl.handle.net/10.1371/journal.pone.0188811
In: PLoS One. Public Library of Science: San Francisco. ISSN 1932-6203; e-ISSN 1932-6203, more
Peer reviewed article  

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Keyword
    Marine

Authors  Top 
  • Moreels, L., more
  • Bhat, C.
  • Vorácová, M.
  • Peigneur, S., more
  • Mäki-Lohiluoma, E.
  • Zahed, F.
  • Pardo, L.A.
  • Yli-Kauhaluoma, J.
  • Kiuru, P.
  • Tytgat, J., more

Abstract
    In the search for novel anticancer drugs, the potassium channel KV10.1 has emerged as an interesting cancer target. Here, we report a new group of KV10.1 inhibitors, namely the purpurealidin analogs. These alkaloids are produced by the Verongida sponges and are known for their wide variety of bioactivities. In this study, we describe the synthesis and characterization of 27 purpurealidin analogs. Structurally, bromine substituents at the central phenyl ring and a methoxy group at the distal phenyl ring seem to enhance the activity on KV10.1. The mechanism of action of the most potent analog 5 was investigated. A shift of the activation curve to more negative potentials and an apparent inactivation was observed. Since KV10.1 inhibitors can be interesting anticancer drug lead compounds, the effect of 5 was evaluated on cancerous and non-cancerous cell lines. Compound 5 showed to be cytotoxic and appeared to induce apoptosis in all the evaluated cell lines.

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