6-Aminoquinolones: photostability, cellular distribution and phototoxicity.

Three selected aminoquinolones endowed with a potent antibacterial (compounds 1 and 2) and antiviral activity (compound 3) have been evaluated for their phototoxic properties in vitro. Photostability studies of these compounds indicate that compound 3 is photostable whereas compound 1 and in particular, compound 2 are rapidly photodegraded upon UVA irradiation, yielding a toxic photoproduct. Intracellular localization of these compounds has been evaluated by means of fluorescence microscopy using tetramethylrhodamine methyl ester and acridine orange, which are specific fluorescent probes for mitochondria and lysosomes, respectively. No co-staining was observed with lysosomal stain for all the test compounds. On the contrary compound 3 was found to be specifically incorporated in mitochondria. The compounds exhibited remarkable phototoxicity in two cell culture lines: human promyelocytic leukaemia (HL-60) and human fibrosarcoma (HT-1080). The quinolone-induced photodamage was also evaluated measuring the photosensitizing cross-linking in erythrocyte ghost membranes, the strand breaks activity and oxidative damage on plasmid DNA. The results show that these derivatives are able to photoinduce crosslink of erythrocytes spectrin, whereas do not significantly photocleavage DNA directly, but single strand breaks were observed after treatment of photosensitized DNA with two base excision repair enzymes, Fpg and Endo III respectively.