Rhynchines A-E: Ca(v)3.1 Calcium Channel Blockers from Uncaria rhynchophylla

Rhynchines A-E (1-5), five new indole alkaloids with an unprecedented skeleton, were isolated from Uncaria rhynchophylla. The new skeleton was characterized by an indole moiety and a 2-oxa-8-azatricyclo[6,5,0(1,5), 0(1,8)]tridecane core, forming a unique 6/5/7/5/5 ring system. Their structures were determined by nuclear magnetic resonance, high-resolution electrospray ionization mass spectrometry, infrared spectroscopy, and calculated electronic circular dichroism (ECD) and were confirmed by X-ray crystallography. Interestingly, 1 and 2 showed strong inhibitory activities against the Ca-v 3.1 calcium channel with IC50 values of 6.86 and 10.41 mu M.