College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou, Henan Province 450001, PR China.
Bioorg Med Chem Lett. 2013 Jun 15;23(12):3505-10. doi: 10.1016/j.bmcl.2013.04.045. Epub 2013 Apr 26.
A series of new strobilurin-pyrimidine analogs were designed and synthesized based on the structures of our previously discovered antiproliferative compounds I and II. Biological evaluation with two human cancer cell lines (A549 and HL60) showed that most of these compounds possessed moderate to potent antiproliferative activity. Two potent candidates (8f, IC50=2.2 nM and 11d, IC50=3.4 nM) were identified with nanomolar activity against leukemia cancer cell line HL60 for further development. This activity represents a 1000- to 2500-fold improvement compared to the parent compounds I and II and is 20- to 30-fold better than the chemotherapy drug, doxorubicin. The present work provides strong incentive for further development of these strobilurin-pyrimidine analogs as potential antitumor agents for the treatment of leukemia.
基于我们之前发现的具有抗增殖活性的化合物 I 和 II 的结构，设计并合成了一系列新型的烯丙基嘧啶类似物。用两种人癌细胞系（A549 和 HL60）进行的生物评价表明，大多数这些化合物具有中等至较强的抗增殖活性。两个有潜力的候选化合物（8f，IC50=2.2 nM 和 11d，IC50=3.4 nM）对白血病癌细胞系 HL60 具有纳摩尔级的活性，可进一步开发。与母体化合物 I 和 II 相比，这种活性提高了 1000 到 2500 倍，比化疗药物阿霉素（doxorubicin）好 20 到 30 倍。本工作为进一步开发这些烯丙基嘧啶类似物作为治疗白血病的潜在抗肿瘤药物提供了有力的动力。
