Guttiferone A Aggregates Modulate Silent Information Regulator 1 (SIRT1) Activity

Natural products guttiferone A, hyperforin, and aristoforin were able to inhibit or increase SIRT1 catalytic activity, depending on protein concentration and presence of detergent. On the basis of NMR data for guttiferone A, we demonstrated that the aggregation state of the natural product played a crucial role for its interaction with the enzyme. These results are useful to interpret future in vitro structure–activity relationship studies on these natural products in the quest of their biological target(s).