New microtubule polymerization inhibitors comprising a nitrooxymethylphenyl group
New microtubule polymerization inhibitors comprising a nitrooxymethylphenyl group
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包含硝基氧基甲基苯基的新型微管聚合抑制剂
DOI：
10.1016/j.bmc.2011.05.031
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发表时间：
2011
期刊：
影响因子：
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他5名
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文献类型：
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作者：
Y.Kawaratani;T.Harada;Y.Hirata;Y.Nagaoka;S.Uesato;他5名
我们已经设计了癌症抗增殖化合物，从苯胺或苯酚衍生物开始，其包含一个或两个硝基氧基甲基苯基，如混合药物NCX 4040和NCX 530。具有对硝基氧甲基苯甲酰基-氧基和-氨基基团的化合物2a以及具有对硝基氧甲基苯甲酰基氨基基团的化合物8a显示出比NCX 4040更有希望的抗人结肠癌和乳腺癌细胞的作用。由于2a和8a而非NCX 4040将人结肠癌HCT 116细胞阻滞在M期，因此前两种化合物可能与NCX 4040不同地抑制细胞生长。人纤维肉瘤HT 1080细胞中α-微管蛋白免疫荧光染色和Hoechst染色的细胞核图像显示，2a和8a破坏微管形成，就像微管蛋白聚合抑制剂长春新碱一样。在体内实验中，以80 mg/kg/天的剂量腹膜内给予8a，使裸鼠中HCT 116异种移植物的生长降低至T/C55%。
We have designed cancer antiproliferative compounds, starting from aniline or phenol derivative, which comprise one or two nitrooxymethylphenyl groups as do the hybrid drugs NCX4040 and NCX530. Compound2awithp-nitrooxymethylbenzoyl-oxy and -amino groups as well as8awith ap-nitrooxymethylbenzoylamino group showed more promising effects than NCX4040 against human colon and breast cancer cells. Since2aand8a, but not NCX4040, arrested human colon carcinoma HCT116 cells in the M phase, the former two compounds may inhibit cell growth differently from NCX4040. Merged images of immunofluorescence-stained α-tubulin and Hoechst-stained nuclei in human fibrosarcoma HT1080 cells showed that2aand8adisrupted microtubule formation just as did vincristine, the tubulin polymerization inhibitor. In experiments in vivo, the intraperitoneal administration of8aat 80 mg/kg/day reduced the growth of HCT116 xenografts in nude mice toT/C55%.