title: Synthesis and biological activity of stable and potent antitumor agents, aniline nitrogen mustards linked to 9-anilinoacridines via a urea linkage.
abstract: To improve the chemical stability and therapeutic efficacy of N-mustard, a series of phenyl N-mustard linked to DNA-affinic 9-anilinoacridines and acridine via a urea linker were synthesized and evaluated for antitumor studies. The new N-mustard derivatives were prepared by the reaction of 4-bis(2-chloroethyl)aminophenyl isocyanate with a variety of 9-anilinoacridines or 9-aminoacridine. The antitumor studies revealed that these agents exhibited potent cytotoxicity in vitro without cross-resistance to taxol or vinblastine and showed potent antitumor therapeutic efficacy in nude mice against human tumor xenografts. It also showed that 24d was capable of inducing marked dose-dependent levels of DNA cross-linking by comet assay and has long half-life in rat plasma.
authors.affiliation: Institute of Biomedical Sciences, Laboratory of Bioorganic Chemistry, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Naval
authors.initials: N
authors.lastname: Kapuriya
authors.forename: Kalpana
authors.initials: K
authors.lastname: Kapuriya
authors.forename: Xiuguo
authors.initials: X
authors.lastname: Zhang
authors.forename: Ting-Chao
authors.initials: TC
authors.lastname: Chou
authors.forename: Rajesh
authors.initials: R
authors.lastname: Kakadiya
authors.forename: Yu-Tse
authors.initials: YT
authors.lastname: Wu
authors.forename: Tung-Hu
authors.initials: TH
authors.lastname: Tsai
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Chen
authors.forename: Te-Chang
authors.initials: TC
authors.lastname: Lee
authors.forename: Anamik
authors.initials: A
authors.lastname: Shah
authors.forename: Yogesh
authors.initials: Y
authors.lastname: Naliapara
authors.forename: Tsann-Long
authors.initials: TL
authors.lastname: Su
mesh_terms: D000166:Acridines / Q000737:chemistry; D000677:Amsacrine / Q000031:analogs & derivatives* / Q000737:chemistry; D000816:Aniline Mustard / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D051381:Rats; D013237:Stereoisomerism; D014508:Urea / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000166:Acridines; D000970:Antineoplastic Agents; D000677:Amsacrine; C022202:9-anilinoacridine; D014508:Urea; D004247:DNA; D000816:Aniline Mustard