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

Lien Moreels, Chinmaya Bhat, Manuela Voráčová, Steve Peigneur, Hannah Goovaerts, Eero Mäki-Lohiluoma, Farrah Zahed, Luis A. Pardo, Jari Tapani Yli-Kauhaluoma, Paula Sinikka Kiuru, Jan Tytgat

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu


In the search for novel anticancer drugs, the potassium channel K(V)10.1 has emerged as an interesting cancer target. Here, we report a new group of K(V)10.1 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 K(V)10.1. 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 K(V)10.1 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.
LehtiPLoS One
DOI - pysyväislinkit
TilaJulkaistu - 8 joulukuuta 2017
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu


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