Discovery and Anticancer Activity of the Plagiochilins from the Liverwort Genus Plagiochila

Abstract

The present analysis retraces the discovery of plagiochilins A-to-W, a series of seco-aromadendrane-type sesquiterpenes isolated from diverse leafy liverworts of the genus Plagiochila. Between 1978, with the first isolation of the leader product plagiochilin A from P. yokogurensis, and 2005, with the characterization of plagiochilin X from P. asplenioides, a set of 24 plagiochilins and several derivatives (plagiochilide, plagiochilal A-B) has been isolated and characterized. Analogue compounds recently described are also evoked, such as the plagiochianins and plagicosins. All these compounds have been little studied from a pharmacological viewpoint. However, plagiochilins A and C have revealed marked antiproliferative activities against cultured cancer cells. Plagiochilin A functions as an inhibitor of the termination phase of cytokinesis: the membrane abscission stage. This unique, innovative mechanism of action, coupled with its marked anticancer action, notably against prostate cancer cells, make plagiochilin A an interesting lead molecule for the development of novel anticancer agents. There are known options to increase its potency, as deduced from structure–activity relationships. The analysis shed light on this family of bryophyte species and the little-known group of bioactive terpenoid plagiochilins. Plagiochilin A and derivatives shall be further exploited for the design of novel anticancer targeting the cytokinesis pathway.