A New 1,2-Naphthoquinone Derivative with Anti-lung Cancer Activity

1,2-Naphthoquinone (2-NQ) is a nucleophile acceptor that non-selectively makes covalent bonds with cys-teine residues in various cellular proteins, and is also found in diesel exhaust, an air pollutant. This molecule has rarely been considered as a pharmacophore of bioactive compounds, in contrast to 1,4-naphthoquinone. We herein designed and synthesized a compound named N-(7,8-dioxo-7,8-dihydronaphthalen-1-yl)-2-methoxybenzamide (MBNQ), in which 2-NQ was hybridized with the nuclear factor-KB (NF-kappa B) inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) as a nucleophile acceptor. Although 50 mu M MBNQ did not inhibit NF-kappa B signaling, 10 mu M MBNQ induced cell death in the lung cancer cell line A549, which was in-sensitive to 2-NQ (10 mu M). In contrast, MBNQ was less toxic in normal lung cells than 2-NQ. A mechanistic study showed that MBNQ mainly induced apoptosis, presumably via the activation of p38 mitogen-activated protein kinase (MAPK). Collectively, the present results demonstrate that the introduction of an appropri-ate substituent into 2-NQ constitutes a new biologically active entity, which will lead to the development of 2-NQ-based drugs.