4-(5H-嘧啶并[5,4-b]吲哚-2-基-氨基)苯甲酰胺类化合物的设计、合成及抗肿瘤活性研究
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摘要
设计、合成了19个未见文献报道的4-(5H-嘧啶并[5,4-b]吲哚-2-基-氨基)苯甲酰胺类衍生物,所有化合物结构均经~1H NMR、~(13)C NMR及HRMS确认。采用噻唑蓝(MTT)法测试了目标化合物对人结肠癌细胞(HCT116)、人乳腺癌细胞(MD-MBA-231)、大鼠神经胶质瘤细胞(C6)、人非小细胞肺癌细胞(A549)、人乳腺癌细胞(MCF-7)的体外抗肿瘤活性。所有化合物均表现出较好的抗肿瘤活性,其中5a、5b、5c、5e、5i、5p和5r对多个细胞株的抑制活性为阳性对照药品5-氟尿嘧啶的20～100倍;其中,以5b的抗肿瘤活性最为突出,对肿瘤细胞HCT116、MD-MBA-231、C6、A549、MCF-7的IC_(50)分别为3. 26、3. 06、0. 63、0. 68、2. 32μmol/L。初步研究结果表明,此类化合物对肿瘤细胞增殖有明显抑制作用,为新型抗肿瘤化合物的设计、合成提供了思路。
Nineteen kinds of novel 4-( 5 H-pyrimido[5,4-b]indol-2-yl-amino) benzamine derivatives were synthesized and evaluated for their in vitro antiproliferative activities. The structures of the as-synthesized compounds were confirmed by ~1 H NMR,~(13)C NMR and HRMS. Their anti-tumor activity against HCT116,MD-MBA-231,C6,A549 and MCF-7 cancer cell lines were tested by MTT assay. All compounds showed good anti-tumor activity,especially compounds 5a,5b,5c,5e,5i,5p and 5r showed 20 to 100 folds activity enhancement than the positive control 5-fluorouracil. The IC_(50) values of 5 b for tumor cells HCT116,MD-MBA-231,C6,A549 and MCF-7 were3. 26,3. 06,0. 63,0. 68,2. 32 μmol/L,respectively. Preliminary results indicated that these compounds have significant inhibitory effects on tumor cell proliferation and provide ideas for the design and synthesis of novel 5 Hpyrimido[5,4-b]indol-2-amine based antitumor compounds.
Nineteen kinds of novel 4-( 5 H-pyrimido[5,4-b]indol-2-yl-amino) benzamine derivatives were synthesized and evaluated for their in vitro antiproliferative activities. The structures of the as-synthesized compounds were confirmed by ~1 H NMR,~(13)C NMR and HRMS. Their anti-tumor activity against HCT116,MD-MBA-231,C6,A549 and MCF-7 cancer cell lines were tested by MTT assay. All compounds showed good anti-tumor activity,especially compounds 5a,5b,5c,5e,5i,5p and 5r showed 20 to 100 folds activity enhancement than the positive control 5-fluorouracil. The IC_(50) values of 5 b for tumor cells HCT116,MD-MBA-231,C6,A549 and MCF-7 were3. 26,3. 06,0. 63,0. 68,2. 32 μmol/L,respectively. Preliminary results indicated that these compounds have significant inhibitory effects on tumor cell proliferation and provide ideas for the design and synthesis of novel 5 Hpyrimido[5,4-b]indol-2-amine based antitumor compounds.
引文
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