Tumour cell population growth inhibition and cell death induction of functionalized 6-aminoquinolone derivatives

Objectives A number of previous studies has provided evidence that the well‐known anti‐bacterial quinolones may have potential as anti‐cancer drugs. The aim of this study was to evaluate potential anti‐tumour activity and selectivity of a set of 6‐aminoquinolones showing some chemical similarity to naphthyridone derivative CX‐5461, recently described as innovative anti‐cancer agent. Materials and methods In‐house quinolones 1‐8 and ad hoc synthesized derivatives 9‐13 were tested on Michigan Cancer Foundation‐7 (MCF‐7) breast cancer cells and mesenchymal progenitor (MePR2B) cell lines, analysing their effects on the cell cycle and cell death using FACS methodology. Activation of p53 was evaluated by western blotting. Results Benzyl esters 4, 5 and their amide counterparts 12, 13 drastically modulated MCF‐7 cell cycles inducing DNA fragmentation and cell death, thus proving to be potential anti‐tumour compounds. When assayed in non‐tumour MePR2B cells, compounds 4 and 5 were cytotoxic while 12 and 13 had a certain degree of selectivity, with compound 12 emerging as the most promising. Western blot analysis revealed that severe p53‐K382ac activation was promoted by benzylester 5. In contrast, amide 12 exerted only a moderate effect which was, however, comparable to that of suberoylanilide hydoxamic acid (SAHA). Conclusions Taken together, these results further reinforce evidence that quinolones have potential as anti‐cancer agents. Future work will be focused on understanding compound 12 mechanisms of action, and to obtain more potent and selective compounds.