Embelin is a natural product, inhibitor of XIAP (X-chromosome-linked Inhibitor of APoptosis) with strong
proapoptotic properties on cancer cells. In order to clarify the role of two OH groups on benzoquinone core, we have prepared
by hemisynthesis close analogs of embelin, where these OH groups have been replaced in a systematic manner by
OMe and OAc groups. Proapoptotic activities of six embelin derivatives have been studied as single agent, or in combination
with TRAIL, and their abilities to interact with XIAP have been evaluated by Surface Plasmon Biacore. Our results
show that these new embelin analogs have good proapoptotic properties against selected cancer cells, often higher than
the natural product itself. Further, this activity is not directly mediated by XIAP. Altogether these preliminary results
demonstrate that for active embelin analogs, the two OH groups are not absolutely required for anticancer activity, opening
new possibilities for the design of proapoptotic derivatives in these series.
Keywords: Apoptosis, Cancer, Embelin, Hemisynthesis, Natural Products, XIAP.
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