A recent approach in anticancer chemotherapy envisages telomerase as a potentially useful target. An attractive strategy
deals with the development of compounds able to stabilize telomeric DNA in the G-quadruplex folded structure and, among them, a
prominent position is found in the perylenes. With the aim to further investigate the role of drug structure, in view of possible pharmaceutical
applications, we synthesized a series of compounds related to PIPER, a well-known perylene-based telomerase inhibitor.
We modified the number of condensed aromatic rings and introduced different side chains to modulate drug protonation state and
extent of self-aggregation. Effective telomerase inhibition was induced by heptacyclic analogues only, some showing a remarkably
wide selectivity index with reference to inhibition of Taq polymerase. G-quadruplex stabilization was monitored by circular dichroism
and melting experiments. Cell cytotoxicity measurements indicated a poor short-term cell killing ability for the best G-quartet
binders. Besides the presence of a planar seven-condensed ring system, the introduction of a cyclic amine in the side chains critically
affects the selectivity window
