Telomerase is a ribonucleoprotein enzyme that catalyzes the addition of repetitive sequences of nucleotides to the ends of chromosomes. Because telomerase is implicated in the unlimited proliferative ability of cancer and is highly upregulated in cancer cells, telomerase inhibition has attracted significant interest as a promising strategy for cancer therapy. Small molecule, non-nucleoside compounds that target the active site of human telomerase reverse transcriptase (hTERT) have significant potential in telomerase inhibition. However, this mode of telomerase inhibition has been underexplored. Chrolactomycin, a natural product isolated in 2001 from a Streptomyces strain, displays inhibition of telomerase in human cancer cell lines. The molecular mode of action for this natural product has not been confirmed, and no syntheses of chrolactomycin have been reported to date. Cheminformatic analysis of chrolactomycin and its hypothesized molecular target has identified a library of de novo small molecule structures that are predicted to act as telomerase inhibitors. The chemical synthesis and biological evaluation of these structures has yielded preliminary structure-activity relationship data and identified small molecules with promising telomerase inhibition activity.

Studies toward the total synthesis of chrolactomycin and the development of novel small molecule telomerase inhibitors

249th National Meeting (2015)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.