Structure-activity relationships among guanine-quadruplex telomerase inhibitors

The ribonucleoprotein telomerase is responsible for maintaining the length of telomeric ends of chromosomes in tumour cells. It is activated in over 8 5% of the tumour cells, and is emerging as a major target for cancer chemot herapy. A range of molecules containing tricyclic and tetracyclic aromatic chromophores has been shown to inhibit the telomerase enzyme system at the micromolar level. There is evidence that they do so via stabilisation of a guanine-quadruplex structure, which provides a stop signal for further telo mere elongation. The known structure-activity relationships for these compo unds are summarised, and pointers for the development of future molecules w ith enhanced selectivity are described. (C) 2000 Elsevier Science Inc. All rights reserved.