Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung 40402, Taiwan, ROC.
Bioorg Med Chem Lett. 2013 Sep 15;23(18):5223-7. doi: 10.1016/j.bmcl.2013.06.083. Epub 2013 Jul 4.
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 physicochemically stable hydrophilic prodrug. Compound 6h is proposed as a new anticancer lead compound.
新型 6-(或 6,7-)取代的 2-(羟基取代苯基)喹啉-4-酮衍生物被合成并筛选对癌细胞系的抗增殖作用。建立了构效关系相关性，最有前途的化合物 2-(3-羟基-5-甲氧基苯基)-6-吡咯烷-1-基喹啉-4-酮(6h)对各种人类癌细胞系，特别是非小细胞肺癌 NCI-H522 表现出强烈的抑制活性。进一步的研究表明，其作用机制类似于抗有丝分裂药物长春新碱。6h 中 C 环 OH 基团的存在将允许该化合物容易转化为水溶性和物理化学稳定的亲水性前药。化合物 6h 被提议为一种新的抗癌先导化合物。
