Wang Yubin, Liu Haitao, Lu Peng, Mao Rui, Xue Xiaojian, Fan Chen, She Jinxiong
Sino-American Institute of Translational Medicine, School of Pharmaceutical Sciences, Nanjing Tech University, No 5. Xinmofan Road, Nanjing, 210009, China.
Center for Biotechnology and Genomic Medicine, Medicinal College of Georgia, Georgia Regents University, 1120 15th ST, Augusta, GA, 30912, USA.
Chem Biol Drug Des. 2015 Oct;86(4):637-47. doi: 10.1111/cbdd.12531. Epub 2015 Mar 1.
Twenty-seven 3, 7-disubstituted coumarin derivatives were designed, synthesized, and evaluated in vitro as anticancer agents. Most of the compounds showed moderate-to-potent antiproliferative activity against K562 cells. Compounds 7b and 7d were chosen to evaluate the concentration of 50% growth inhibition (GI50 ) against SN12C, OVCAR, BxPC-3, KATO-III, T24, SNU-1, WiDr, HeLa, K562, and AGS cell lines. The most potent compound 7d was selected for further cell cycle arrest assay in the AGS cell line. The in vitro data indicated that methylation of benzimidazole moiety at the 3-position of coumarin exhibited significant enhancement of anticancer activity. This study should provide important information for further modification and optimization of coumarin derivatives as anticancer agents.
设计、合成了27种3,7 - 二取代香豆素衍生物，并对其进行了体外抗癌活性评估。大多数化合物对K562细胞显示出中度至强效的抗增殖活性。选择化合物7b和7d评估其对SN12C、OVCAR、BxPC - 3、KATO - III、T24、SNU - 1、WiDr、HeLa、K562和AGS细胞系的50%生长抑制浓度（GI50）。选择最具活性的化合物7d在AGS细胞系中进行进一步的细胞周期阻滞测定。体外数据表明，香豆素3位苯并咪唑部分的甲基化显著增强了抗癌活性。本研究应为香豆素衍生物作为抗癌药物的进一步修饰和优化提供重要信息。
