Key Laboratory of Pesticide Chemistry and Application, Ministry of Agriculture, Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, People's Republic of China.
Eur J Med Chem. 2010 Dec;45(12):5576-84. doi: 10.1016/j.ejmech.2010.09.007. Epub 2010 Sep 17.
A pair of chemical isomeric structures of N-acylhydrazone compounds I and II were designed and synthesized. The reaction was carried out with high diastereoselectivity to obtain one configurational isomer in excellent yields. The exact configuration and conformation of IIa and IIe were confirmed by the X-ray single crystal diffraction. The antitumor bioassay revealed that some compounds exhibited excellent activity against the selected cancer cell lines. In particular, IIf (IC50=16.4 μM) was better than doxorubicin (IC50=53.3 μM) against human promyelocytic leukemic cells (HL-60). Their toxicities were predicted in silico. The results showed that compounds II were safe and eligible to be development candidates. IIf showed great promise as a novel lead compound for further anticancer discovery.
一对 N-酰腙化合物 I 和 II 的化学非对映异构体结构被设计和合成。反应具有高的非对映选择性，以优异的产率获得一个构型异构体。通过 X 射线单晶衍射确证了 IIa 和 IIe 的确切构型和构象。抗肿瘤生物测定表明，一些化合物对所选癌细胞系表现出优异的活性。特别是，化合物 IIf（IC50=16.4 μM）对人早幼粒细胞白血病细胞（HL-60）的活性优于阿霉素（IC50=53.3 μM）。通过计算机预测了它们的毒性。结果表明，化合物 II 是安全的，有资格成为开发候选物。IIf 作为一种新型的抗癌发现的先导化合物具有很大的潜力。
