Synthesis and in vitro cytotoxicity of 9-anilinoacridines bearing N-mustard residue on both anilino and acridine rings.
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.
Chen
Ching-Huang
CH
Laboratory of Bioorganic Chemistry, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Lin
Yi-Wen
YW
Zhang
Xiuguo
X
Chou
Ting-Chao
TC
Tsai
Tsong-Jen
TJ
Kapuriya
Naval
N
Kakadiya
Rajesh
R
Su
Tsann-Long
TL