The dichapetalins and dichapetalin-type compounds: structural diversity, bioactivity, and future research perspectives†

Covering mainly from 2013 up to 2023 with relevant references to work done before 2013

First reported in 1995, the dichapetalins and analogous compounds constitute a novel class of natural dammarane-type merotriterpenoids characterized by their unique 2-phenylpyrano moiety annellated to ring A of the dammarane skeleton. They have been reported from only two genera: Dichapetalum (Dichapetalaceae) and Phyllanthus (Phyllanthaceae). About 100 novel dichapetalins and dichapetalin-type compounds, including the acutissimatriterpenes and their antitumour and other bioactivities have been reported. In the present review, we cover the distribution, ethnobotanical and medicinal importance and the diversity of secondary metabolites reported from the two genera Dichapetalum and Phyllanthus from 2013 to date, with appropriate reference to relevant information prior to 2013. We also propose and discuss possible biosynthetic pathways, antitumour activity against a broad range of human and murine cancer cell lines, structure activity relationships, and other biological activities and mechanisms of action. Finally, the review deals with future perspectives which include expansion of the structural diversity and bioactivity scope, possible simplification of the structural complexity of the compounds to enhance their drug-likeness, in silico studies, and continuation of the search for new dichapetalins and dichapetalin-type compounds from the over 200 Dichapetalum and over 1200 Phyllanthus species yet to be investigated. It is envisaged that the present review will stimulate further multidisciplinary and interdisciplinary studies.