Design and Synthesis of Telomestatin Derivatives and Their Inhibitory Activity of Telomerase

Abstract

Telomestatin derivatives of 2a-2c, which have macrocyclic bisamide structure, were designed and synthesized.One of these compounds (2a) showed inhibitory activity of telomerase with an IC 50 of 2 µM.Telomestatin (1) is a natural product isolated from Streptomyces anulatus 3533-SV4 by the screening of Telomeric Repeat Amplification Protocol (TRAP) assay. 1 Telomestatin (1) shows potent telomerase inhibitory activity with an IC 50 of 5 nM, and it also has been realized to stabilize strongly the telomeric G-quadruplex formation. 2Thus, telomestatin (1) appears to be an ideal lead compound for the telomere-targeted anticancer agent. 3,