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.
Highlights
Many efforts have been made to prevent and treat cancer, it is still one of the leading causes of death worldwide, with 8.8 million cancer deaths in 2015 [1]
Synthesis of the simplified purpurealidin analogs was based on the amide coupling of purpurealidin E 4 or tyramine derivative 11 with aromatic carboxylic acids
We investigated if simplified synthetic analogs of purpurealidins are able to inhibit the oncogenic potassium channel KV10.1 and if they exert antineoplastic effect on cancer cell lines
Summary
Many efforts have been made to prevent and treat cancer, it is still one of the leading causes of death worldwide, with 8.8 million cancer deaths in 2015 [1]. A targeted approach as used in precision or personalized medicine could enhance the specificity of the treatment and minimize the negative side effects. The voltage-gated potassium channel human ether à go-go 1 (hEag, KV10.1) represents an interesting cancer target because of its ectopic expression in over 70% of human cancers [2]. KV10.1 inhibitors are considered to be lead compounds in the development of novel anticancer drugs [2]. In order to identify novel KV10.1 inhibitors or modulators, the effect of synthetic bromotyramine alkaloids on KV10.1-expressing oocytes was electrophysiologically investigated
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
