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