2. Universidad Cardenal Herrera-CEU

Two new ligands (TPB3P and TPB3Py) showing a strong stabilisation effect and good selectivity for G4 over duplex DNAs have been synthesised. The ligands hold three analogous polyamine pendant arms (TPA3P and TPA3Py) but differ in the central aromatic core, which is a triphenylbenzene moiety instead of a triphenylamine moiety. Both TPB3P and TPB3Py exhibit high cytotoxicity in MCF-7, LN229 and HeLa cancer cells in contrast to TPA-based ligands, which exhibit no significant cytotoxicity. Moreover, the most potent G4 binders have been encapsulated in liposomes and AS1411 aptamer-targeted liposomes reaching nanomolar IC50 values for the most cytotoxic systems.

The interaction of a polyazacyclophane ligand having an ethylamine pendant arm functionalized with an anthryl group (L), with the single-stranded polynucleotides polyA, polyG, polyU, and polyC as well as with the double-stranded polynucleotides polyA–polyU, poly(dAT)2, and poly(dGC)2 has been followed by UV/Vis titration, steady state fluorescence spectroscopy, and thermal denaturation measurements. In the case of the single-stranded polynucleotides, the UV/Vis and fluorescence titrations permit to distinguish between sequences containing purine and pyrimidine bases. For the double-stranded polynucleotides the UV/Vis measurements show for all of them hypochromicity and bathochromic shifts. However, the fluorescence studies reveal that both polyA–polyU and poly(dAT)2 induce a twofold increase in the fluorescence, whereas interaction of poly(dGC)2 with the ligand L induces a quenching of the fluorescence. Cu2+ modulates the interaction with the double-stranded polynucleotides due to the conformation changes that its coordination induces in compound L. In general, the spectroscopic studies show that intercalation seems to be blocked by the formation of the metal complex. All these features suggest the possibility of using compound L as a sequence-selective fluorescence probe.

Fumagillin-loaded liposomes were injected into ApoE-KO mice. The animals were divided into several groups to test the efficacy of this anti-angiogenic drug for early treatment of atherosclerotic lesions. Statistical analysis of the lesions revealed a decrease in the lesion size after 5 weeks of treatment.