Xia Y, Yang Z Y, Xia P, Hackl T, Hamel E, Mauger A, Wu J H, Lee K H
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599-7360, USA.
J Med Chem. 2001 Nov 8;44(23):3932-6. doi: 10.1021/jm0101085.
Fluorinated 2-phenyl-4-quinolone derivatives were synthesized and evaluated in National Cancer Institute's 60 human tumor cell line in vitro screen. From the results, the ketone moiety plays an essential role in activity. Among the compounds tested, 2'-fluoro-6-pyrrol-2-phenyl-4-quinolone (13) exhibited the most potent cytotoxic activities (log GI(50) < -8.00) against renal and melanoma tumor cell lines. Compound 13 was also a potent inhibitor of tubulin polymerization (IC(50) = 0.46 microM) and of radiolabeled colchicine binding to tubulin, with activities comparable to those of the potent antimitotic natural products colchicine, podophyllotoxin, and combretastatin A-4.
合成了氟化2-苯基-4-喹诺酮衍生物，并在美国国立癌症研究所的60种人肿瘤细胞系体外筛选中进行了评估。从结果来看，酮部分在活性中起着至关重要的作用。在所测试的化合物中，2'-氟-6-吡咯-2-苯基-4-喹诺酮（13）对肾和黑色素瘤肿瘤细胞系表现出最有效的细胞毒性活性（log GI(50) < -8.00）。化合物13也是微管蛋白聚合的有效抑制剂（IC(50) = 0.46 microM）以及放射性标记秋水仙碱与微管蛋白结合的有效抑制剂，其活性与强效抗有丝分裂天然产物秋水仙碱、鬼臼毒素和康普瑞他汀A-4相当。
