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

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Moreels , L , Bhat , C , Voráčová , M , Peigneur , S , Goovaerts , H , Mäki-Lohiluoma , E , Zahed , F , Pardo , L A , Yli-Kauhaluoma , J T , Kiuru , P S & Tytgat , J 2017 , ' Synthesis of novel purpurealidin analogs and evaluation of their effect on the cancer-relevant potassium channel K V 10.1 ' PLoS One , vol 12 , no. 12 , 0188811 . DOI: 10.1371/journal.pone.0188811

Title: Synthesis of novel purpurealidin analogs and evaluation of their effect on the cancer-relevant potassium channel KV10.1
Author: Moreels, Lien; Bhat, Chinmaya; Voráčová, Manuela; Peigneur, Steve; Goovaerts, Hannah; Mäki-Lohiluoma, Eero; Zahed, Farrah; Pardo, Luis A.; Yli-Kauhaluoma, Jari Tapani; Kiuru, Paula Sinikka; Tytgat, Jan
Contributor: University of Helsinki, Faculty of Pharmacy
University of Helsinki, Faculty of Pharmacy
Belongs to series: PLoS One
ISSN: 1932-6203
Abstract: 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.
URI: http://hdl.handle.net/10138/230185
Date: 2017-12-08
Subject: 317 Pharmacy
SPONGE PSAMMAPLYSILLA-PURPU REA
MARINE SPONGE
BROMOTYROSINE ALKALOIDS
CANCER
METABOLITES
APOPTOSIS
CELLS
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