Synthesis and in vitro and in vivo antitumor activity of 2-phenylpyrroloquinolin-4-ones.
Maria Grazia Ferlin, Gianfranco Chiarelotto, Venusia Gasparotto, Lisa Dalla Via, Vincenzo Pezzi, Luisa Barzon, Giorgio Palù, Ignazio Castagliuolo
文献索引：J. Med. Chem. 48(9) , 3417-27, (2005)
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摘要
In our search for potential new anticancer drugs, we designed and synthesized a series of tricyclic compounds containing the antimitotic 2-phenylazaflavone chromophore fused to a pyrrole ring in a pyrroloquinoline structure. Compounds 8, 18, 19, 22, 23, 25 and 26, when tested against a panel of fourteen human tumor cell lines, showed poor in vitro cytotoxic activity, whereas 20, 21 and 24 showed significant activity (IC(50) 0.7 to 50 microM). Steroid hormone-sensitive ovary, liver, breast and adrenal gland adenocarcinoma cell lines displayed the highest sensitivity (IC(50) 0.7 to 8 microM). Compound 24 blocked cells in the G(2)/M phase of the cell cycle and induced a significant increase in apoptotis. Compounds 20, 21 and 24 proved to alter microtubule assembly and stability, displaying a cytoplasmic microtubule network similar to that caused by Vincristine. In vivo, administration of compound 24 to Balb/c mice inhibited the growth of a syngenic hepatocellular carcinoma.
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