Another interesting
feature that might explain the difference of affinity is that the second
binding mode is more deeply inserted in the cavity of the S4
fragment of hERG channel. This way, nukuhivensium and N12-
methylnukuhivensium are much closer to the center of the channel
and thus carry a positive charge toward the central hole of the channel
which might disturb more intensively the ionic transport of
potassium (Fig. 8). From these results, we deduce a pharmacophore
scheme which might explain the inhibiting activity of the alkaloids.
This one gathers all the above-cited favorable interacting patterns
(aromatic moiety, positive charge and alkyl chain) and might be
useful for further drug-design studies.