SYNTHESIS OF G-QUADRUPLEX LIGANDS AS POTENTIAL TELOMERASE INHIBITORS

Herein it is described the goal of the proposed research, which is the synthesis of model phenanthroline derivatives, capable of stabilizing the G-quadruplex structure and interfering with the action of telomerase. The human single stranded telomere end can potentially fold into a number of four-repeat quadruplexes. Stabilization of these quadruplexes by small molecules will destabilize telomere maintainance in cancer cells and lead to potential agents capable of destroying cancerous growth. A number of other novel acridine derivatives, know as topoisomerase inhibitors and relative cytotoxic activity on different cell lines has also been investigated. This class of compounds is potentially capable of forming a stable complex with DNA-topoisomerase, which prevents the enzyme from completing his cycle, therefore causing destabilization, protein disruption or denaturation. Most of the newly synthesized compounds reveal a high DNA affinity, an excellent cytotoxic potency and interesting preliminary in vivo activity