Synthesis and cytotoxicity of pyrido[4,3-b]carbazole alkaloids against HCT-116 and HL-60 cells

被引:12
|
作者
Itoh, Tomoki [1 ]
Hatae, Noriyuki [1 ]
Nishiyama, Takashi [2 ,3 ]
Choshi, Tominari [2 ,3 ]
Hibino, Satoshi [2 ,3 ]
Yoshimura, Teruki [1 ]
Ishikura, Minoru [1 ]
机构
[1] Hlth Sci Univ Hokkaido, Sch Pharmaceut Sci, Ishikari, Hokkaido 0610293, Japan
[2] Fukuyama Univ, Grad Sch Pharm & Pharmaceut Sci, Fukuyama, Hiroshima 7290292, Japan
[3] Fukuyama Univ, Fac Pharm & Pharmaceut Sci, Fukuyama, Hiroshima 7290292, Japan
关键词
Pyrido[4,3-b]carbazole alkaloids; Cytotoxicity; HCT-116; cell; HL-60; ELLIPTICINE DERIVATIVES; INTERCALATIVE BINDING; ANTICANCER AGENTS; ANTITUMOR AGENTS; DNA; OLIVACINE; APOPTOSIS; ANALOGS; SERIES;
D O I
10.1007/s00044-017-2068-6
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Ellipticine, olivacine, and their five reduced natural variants were synthesized via a palladium-catalyzed tandem cyclization/cross-coupling reaction as the key step. In addition, a previously unknown conformer of janetine was obtained through conformational inversion of the D ring in janetine. Because there are few synthetic approaches for reduced natural variants, little is known about the biological activities of these compounds. Six synthetic natural alkaloids and five of their derivatives were evaluated for their antiproliferative activity against HCT-116 and HL-60 cells. The activities of variants with the D-reduced ring or without the C(11)-Me group were lower than those of ellipticine. The conformer of guatambuine showed higher activities than guatambuine.
引用
收藏
页码:412 / 419
页数:8
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