THE DISCOVERY OF NEW KINGIANIC ACIDS FROM ENDIANDRA KINGIANA WITH POTENTIAL ANTICANCER ACTIVITY

In our pursuit of discovering bioactive phytochemicals from the Malaysia flora, we recently reported a series of new natural pentacyclic polyketides, kingianins A-L, isolated from the ethyl acetate extract of the bark of Endiandra kingiana Gamble (Lauraceae). Several kingianins showed strong binding affinity to the anti-apoptotic protein Bcl-xL, and can therefore be considered as potential anticancer agents.

In order to discover additional members of this chemical series or close analogues, we investigated the methanolic extract of the bark of this species. E. kingiana is a medium-sized evergreen tree, distributed throughout the peninsular Malaysia and Borneo. There are about 125 Endiandra species found through the tropical regions, including 10 species in Malaysia, but to our knowledge only three species i.e E. introrsa, E. anthropophagorum and E. kingiana, have been studied for their phytochemicals. The first one has been reported to produce interesting cyclic polyketides, named endiandric acids, possessing eight chiral centers, and usually isolated as racemic mixtures. It was postulated by Black and co-workers that they could be formed by non-enzymatic cyclizations (8πe and 6πe electrocyclization followed by Diels-Alder reaction) of a phenylpolyene acid precursor.

The aim of this study is to isolate compounds from the methanolic extract of the E. kingiana bark, which further being subjected to MTS cell viability assays on selected human cancer cell lines and binding affinities toward antiapoptotic proteins, namely Bcl-xL and Mcl-1. This effort is to identify compounds with potential anticancer activity.