新型六氢吡啶-2,3-并吲哚化合物的合成及其抗肿瘤活性

以3-取代氧化吲哚与丙烯酸酯为原料,经Michael加成反应制得中间体——3-丙酸酯取代氧化吲哚(3a~3d);3a~3d与甲胺发生酰胺化反应制得3-丙酰胺取代氧化吲哚(4a~4d);4a~4d用氢化铝锂还原-环化,合成了4个六氢吡啶-2,3-并吲哚化合物(5a~5d);5a和5b用氢化铝锂还原合成了2个六氢吡啶-2,3-并吲哚化合物(6a和6b),5a~5d,6a和6b均为新化合物,总产率42%~61%,其结构经~1H NMR,~(13)C NMR和HR-ESIMS表征。采用MTT法研究了5a~5d,6a和6b对人肺癌细胞(A549),人前列腺(PC-3)和人白血病细胞(K562)的体外抗肿瘤活性。结果表明:5b对A549,PC-3和K562的抑制活性均较好,其IC50分别为27.2μmol·L~(-1),37.5μmol·L~(-1)和21.7μmol·L~(-1)。

Synthesis and Anti-tumor Activities of Novel Hexahydro-1H-pyrido[2,3-b] indole Compounds

Four intermediates, 3-propionate oxindole (3a~3d), were obtained by Michael addition , using 3-substituted oxindoles and acrylates as starting materials .3-Propionamide oxindoles (4a~4d) were prepared by the reaction of 3a~3d with methylamine.Four novel hexahydro-1H-pyrido2,3-b] indole compounds(5a~5d) were synthesized by reductive-cyclization from 4a~4d, using LiAlH4 as reductant.Two novel hexahydro-1H-pyrido2,3-b]indole compounds(6a and 6d) were synthesized by reduction of 5a and 5b with LiAlH4 .The overall yield of 5a~5d, 6a and 6b were 42%~61%.The structures were characterized by 1 H NMR, 13 C NMR and HR-ESI-MS.The in vitro anti-tumor activities of 5 and 6 against human prostate cancer cells ( PC-3 ) , human lung cancer cells ( A549 ) and human leukemia cells( K562 ) were investgated by MTT method .The results demonstrated that 5b exhibited better inhibition activity against K562, A549 and PC-3.IC50were 27.2μmol· L-1, 37.5μmol· L-1 and 21.7 μmol· L-1 , respectively .