Linker-modified triamine-linked acridine dimers: synthesis and cytotoxicity properties in vitro and in vivo.
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.
Wang
Shan-Shue
SS
Department of Biochemical Engineering, Kao Yuan University, 1821 Chung-Shan Rd, Lu-Chu Hsiang, Kaohsiung, Taiwan, ROC. sswang@cc.kyu.edu.tw
Lee
Yi-Jen
YJ
Hsu
Shih-Chung
SC
Chang
Hsueh-O
HO
Yin
Wei-Kung
WK
Chang
Lien-Shange
LS
Chou
Shan-Yen
SY
D000166:Acridines / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D004247:DNA / Q000378:metabolism; D006801:Humans; D007202:Indicators and Reagents; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D008813:Mice, Inbred ICR; D016513:Mice, SCID; D009584:Nitrogen / Q000737:chemistry; D010957:Plasmids / Q000187:drug effects / Q000235:genetics; D013329:Structure-Activity Relationship; D013778:Tetrazolium Salts; D013844:Thiazoles
D000166:Acridines; D000970:Antineoplastic Agents; D007202:Indicators and Reagents; D007364:Intercalating Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D004247:DNA; C022616:thiazolyl blue; D009584:Nitrogen