ABSTRACT
The preparation and cytotoxicity properties of a series of N(epsilon)-substituted triamine-linked acridine dimers are described. Most acridine dimer derivatives reveal highly potent in vitro cytotoxicity properties and DNA binding activity. Several acridine dimers were selected to study their action in vivo. These acridine dimers have demonstrated a narrow safe margin, as has adriamycin, but higher maximum tolerate dose (MTD) in comparison with that of adriamycin in ICR mice. The acridine dimers also demonstrated various anit-COLO 205 solid tumor activities in vivo. Compound 1 has shown the most potent solid tumor inhibition.
Subject(s)
Acridines/chemical synthesis , Acridines/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Animals , Cell Line, Tumor , Cell Survival/drug effects , Colonic Neoplasms/drug therapy , Colonic Neoplasms/pathology , DNA/metabolism , Humans , Indicators and Reagents , Intercalating Agents/chemical synthesis , Intercalating Agents/pharmacology , Magnetic Resonance Spectroscopy , Mass Spectrometry , Mice , Mice, Inbred ICR , Mice, SCID , Nitrogen/chemistry , Plasmids/drug effects , Plasmids/genetics , Structure-Activity Relationship , Tetrazolium Salts , ThiazolesABSTRACT
A total synthesis of (+/-)-sarracenin (1) is described. The key steps include (1) regioselective ring expansion of 7 to bicyclo[3.2.1]ketone6 and (2) ring opening of tricyclic ketone 5 to ester 4.
