Human telomerase inhibition by substituted acridine derivatives

R J Harrison; S M Gowan; L R Kelland; S Neidle

doi:10.1016/s0960-894x(99)00394-7

Human telomerase inhibition by substituted acridine derivatives

Bioorg Med Chem Lett. 1999 Sep 6;9(17):2463-8. doi: 10.1016/s0960-894x(99)00394-7.

Authors

R J Harrison¹, S M Gowan, L R Kelland, S Neidle

Affiliation

¹ CRC Biomolecular Structure Unit, The Institute of Cancer Research, Sutton, Surrey, UK.

PMID: 10498189
DOI: 10.1016/s0960-894x(99)00394-7

Abstract

A series of 3,6-disubstituted acridine derivatives have been rationally designed as telomerase inhibitors. They have been designed on the basis that inhibition of telomerase occurs by stabilising G-quadruplex structures formed by the folding of telomeric DNA. The most potent inhibitors have IC50 values against telomerase of between 1.3 and 8 microM, comparable to their cytotoxicity in ovarian cancer cell lines.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acridines / chemistry
Acridines / pharmacology*
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology
Drug Screening Assays, Antitumor
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Humans
Telomerase / antagonists & inhibitors*
Tumor Cells, Cultured

Substances

Acridines
Antineoplastic Agents
Enzyme Inhibitors
Telomerase