Synthesis and biological activity of stable and potent antitumor agents, aniline nitrogen mustards linked to 9-anilinoacridines via a urea linkage.
Basic Information
ID: ALA1150326
Journal: Bioorg Med Chem
Title: Synthesis and biological activity of stable and potent antitumor agents, aniline nitrogen mustards linked to 9-anilinoacridines via a urea linkage.
Authors: Kapuriya N, Kapuriya K, Zhang X, Chou TC, Kakadiya R, Wu YT, Tsai TH, Chen YT, Lee TC, Shah A, Naliapara Y, Su TL.
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.
CiteXplore: 18450456
DOI: 10.1016/j.bmc.2008.04.024
Patent ID: ┄