Prenylflavanones as Novel T-Type Calcium Channel Blockers Useful for Pain Therapy

Prenylated flavonoids have attracted much attention due to their promising and diverse bioactivities on multitarget tissues. To the best of our knowledge, our recent studies demonstrated first that (2S)-6-prenylnaringenin (6-PNG), a hop component, blocks Ca_v3.2 T-type calcium channels (T-channels) and alleviates neuropathic and visceral pain with little side effects; it also indicated first that other natural prenylflavanones (PFVNs), such as sophoraflavanone G and (2S)-8-PNG, or synthetic 6-PFVNs including (2R/S)-6-PNG and its derivatives are capable of blocking T-channels and useful for pain therapy. Through the structure-activity relationship studies on the synthetic 6-PFVNs, we identified 6-(3-ethylpent-2-enyl)-5,7-dihydroxy-2-(2-hydroxyphenyl)chroman-4-one (8j or KTt-45) as the most potent blocker of Ca_v3.2 T-channels. It is interesting to recognize a prenylated flavonoid, belonging to other sub-classes, as a novel T-channel blocker. Therefore, this article will review some of our recent studies to introduce a new branch to researchers studying on prenylated flavonoids.