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  Synthesis of novel purpurealidin analogs and evaluation of their effect on the cancer-relevant potassium channel KV10.1

Moreels, L., Bhat, C., Voráčová, M., Peigneur, S., Goovaerts, H., Mäki-Lohiluoma, E., et al. (2017). Synthesis of novel purpurealidin analogs and evaluation of their effect on the cancer-relevant potassium channel KV10.1. PLOS ONE, 12(12), e0188811. doi:10.1371/journal.pone.0188811.

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Item Permalink: https://hdl.handle.net/21.11116/0000-0009-F253-8 Version Permalink: https://hdl.handle.net/21.11116/0000-0009-F254-7
Genre: Journal Article

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https://doi.org/10.1371/journal.pone.0188811 (Any fulltext)
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Moreels, Lien1, Author
Bhat, Chinmay1, Author
Voráčová, Manuela1, Author
Peigneur, Steve1, Author
Goovaerts, Hannah1, Author
Mäki-Lohiluoma, Eero1, Author
Zahed, Farrah1, Author
Pardo, Luis A.1, Author
Yli-Kauhaluoma, Jari1, Author
Kiuru, Paula1, Author
Tytgat, Jan1, Author
Affiliations:
1Max Planck Society, ou_persistent13              

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Free keywords: 3T3 Cells 4-Butyrolactone/*analogs & derivatives/chemical synthesis/pharmacology Animals Apoptosis/drug effects Cell Line, Tumor Dose-Response Relationship, Drug Drug Screening Assays, Antitumor Ether-A-Go-Go Potassium Channels/*antagonists & inhibitors HEK293 Cells Humans Mice Neoplasms/*pathology Potassium Channel Blockers/*pharmacology
 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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 Dates: 2017-12-08
 Publication Status: Issued
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 Rev. Type: -
 Identifiers: Other: 29220359
DOI: 10.1371/journal.pone.0188811
ISSN: 1932-6203 (Electronic) 1932-6203 (Linking)
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Title: PLOS ONE
Source Genre: Journal
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Pages: - Volume / Issue: 12 (12) Sequence Number: - Start / End Page: e0188811 Identifier: -