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.