Solid-Phase synthesis of a library constructed of aromatic phosphate, long alkyl chains and tryptophane components, and identification of potent dipeptide telomerase inhibitors

Abstract

Telomerase inhibitors are expected as a new candidate of therapeutic agents for cancer. Recently, we have found novel inhibitors based on the bisindole skeleton. In this study, solid-phase synthesis was applied to construct a library of inhibitors having aromatic phosphate, long alkyl chain and tryptophane components, from which a d, d-ditryptophane derivative has been identified as a new potent telomerase inhibitor with IC 50 values of 0.3 μM. A hypothetical binding model for the new inhibitors has been proposed based on the structure–activity relationship.