Design, synthesis, and mechanism of action of 2-(3-hydroxy-5-methoxyphenyl)-6-pyrrolidinylquinolin-4-one as a potent anticancer lead.
Design, synthesis, and mechanism of action of 2-(3-hydroxy-5-methoxyphenyl)-6-pyrrolidinylquinolin-4-one as a potent anticancer lead.
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DOI：
10.1016/j.bmcl.2013.06.083
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发表时间：
2013-09-15
影响因子：
2.7
通讯作者：
Lee, Kuo-Hsiung
中科院分区：
文献类型：
--
作者：
Cheng, Yung-Yi;Liu, Chin-Yu;Tsai, Meng-Tung;Lin, Hui-Yi;Yang, Jai-Sing;Wu, Tian-Shung;Kuo, Sheng-Chu;Huang, Li-Jiau;Lee, Kuo-Hsiung
关键词：
合成了新的6-（或6，7-）取代的2-（羟基取代的苯基）喹啉-4-酮衍生物，并筛选了其对癌细胞系的抗增殖作用。建立了构效关系，并且最有希望的化合物2-（3-羟基-5-甲氧基苯基）-6-吡咯烷-1-基喹啉-4-酮（6 h）对多种人类癌细胞系，特别是非小细胞肺癌NCI-H522表现出强的抑制活性。其他研究表明其作用机制与抗有丝分裂药物长春新碱相似。在6小时内C环OH基团的存在将允许该化合物容易地转化为水溶性和物理化学稳定的亲水性前药。化合物6 h被认为是一个新的抗癌先导化合物。
New 6- (or 6,7-) substituted 2-(hydroxyl substituted phenyl)quinolin-4-one derivatives were synthesized and screened for antiproliferative effects against cancer cell lines. Structure-activity relationship correlations were established and the most promising compound 2-(3-hydroxy-5-methoxyphenyl)-6-pyrrolidin-1-ylquinolin-4-one (6h) exhibited strong inhibitory activity against various human cancer cell lines, particularly non-small cell lung cancer NCI-H522. Additional studies suggested a mechanism of action resembling that of the antimitotic drug vincristine. The presence of a C-ring OH group in 6h will allow this compound to be converted readily to a water soluble and physiochemically stable hydrophilic prodrug. Compound 6h is proposed as a new anticancer lead compound.
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