Synthesis, structure, photophysical, photochemical, and biological properties of hybrid macrocyclic structures containing two naphthalene moieties and a tri(ethylene glycol) tether

The structure of some promising crown ether-paracyclophane hybrid macrocyclic derivatives showing remarkable cytotoxicity was modified by replacing the two phenyl rings with naphthalene units. The synthesis of the newly designed macrocyclic derivatives was accomplished by applying the previously developed CuAAC coupling-dimerization strategy to the previously published naphthalene MBHA derivative 5. Then, the resulting tri(ethylene glycol)-tethered MBHA dimer 6 was reacted with n-butylamine to obtain the mixture of macrocyclic diastereomers 4 in good yields. These diastereomers were separated by flash chromatography and thoroughly characterized from the point of view of their structure, photophysical, photochemical, and biological features. The compounds showed interesting anti-proliferative and pro-apoptotic activities against cancer cells, paving the way to be further developed as antitumor/antiproliferative agents.