Chen Ching-Huang, Lin Yi-Wen, Zhang Xiuguo, Chou Ting-Chao, Tsai Tsong-Jen, Kapuriya Naval, Kakadiya Rajesh, Su Tsann-Long
Laboratory of Bioorganic Chemistry, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Eur J Med Chem. 2009 Jul;44(7):3056-9. doi: 10.1016/j.ejmech.2008.07.016. Epub 2008 Jul 22.
A series of 9-anilinoacridines having an alkylating N-mustard pharmacophore on both anilino (C-3' or C-4') and acridine (C-4) rings with O-ethyl (O-C(2)) or O-butyl (O-C(4)) spacer were synthesized to evaluate their cytotoxicity against human lymphoblastic leukemia (CCRF-CEM) cell growth in vitro. It was revealed that these conjugates exhibited significant in vitro cytotoxicity. Among these agents, compound 13 was the most cytotoxic with IC(50) value of 1.3 nM and is as potent as taxol (IC(50)=1.1 nM). The structure-activity relationship study showed that the length of the spacer and the position of the substituent do affect their cytotoxicity.
合成了一系列在苯胺基（C-3'或C-4'）和吖啶（C-4）环上均带有烷基化N-芥子气药效基团、带有O-乙基（O-C(2)）或O-丁基（O-C(4)）间隔基的9-苯胺基吖啶，以评估它们对人淋巴细胞白血病（CCRF-CEM）细胞体外生长的细胞毒性。结果表明，这些缀合物表现出显著的体外细胞毒性。在这些试剂中，化合物13的细胞毒性最强，IC(50)值为1.3 nM，与紫杉醇的效力相当（IC(50)=1.1 nM）。构效关系研究表明，间隔基的长度和取代基的位置确实会影响它们的细胞毒性。
