کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1363475 | 981513 | 2005 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Synthesis and cytotoxic activity of N-[(alkylamino)alkyl]carboxamide derivatives of 7-oxo-7H-benz[de]anthracene, 7-oxo-7H-naphtho[1,2,3-de]quinoline, and 7-oxo-7H-benzo[e]perimidine Synthesis and cytotoxic activity of N-[(alkylamino)alkyl]carboxamide derivatives of 7-oxo-7H-benz[de]anthracene, 7-oxo-7H-naphtho[1,2,3-de]quinoline, and 7-oxo-7H-benzo[e]perimidine](/preview/png/1363475.png)
7-Oxo-7H-naphtho[1,2,3-de]quinoline-11-carboxamides and analogues were prepared and evaluated for in vitro and in vivo antitumor activity. Chromophore variations included ‘deaza’ (7-oxo-7H-benz[de]anthracene) and ‘diaza’ (7-oxo-7H-benzo[e]perimidine) analogues, and side chain variations included chiral α-methyl compounds. The naphthoquinolines were the most cytotoxic, with IC50 values of 5–20 nM, and showed the strongest DNA binding, with high selectivity for G-C rich DNA. The chiral α-methyl analogues were 10–20-fold more cytotoxic than the parent des-methyl compound. Both enantiomers provided substantial growth delays against s.c. colon 38 tumors in mice, with the R-enantiomer more active than the S (tumor growth delays of >35 and 12 days, respectively).
We discuss the synthesis and structure–cytotoxicity relationships of GC-selective naphthoquinoline-11-carboxamides and analogues. Examples showed high activity in the mouse colon 38 tumor model.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry - Volume 13, Issue 11, 1 June 2005, Pages 3657–3665