3-硝基-1,8-萘酰亚胺类衍生物的设计、合成与生物评价及其作为潜在抗肿瘤药物的研究。
Design, synthesis and biological evaluation of 3-nitro-1,8-naphthalimides as potential antitumor agents.
机构信息
School of Pharmacy, Guilin Medical University, Guilin 541004, China.
School of Pharmacy, Guilin Medical University, Guilin 541004, China.
出版信息
Bioorg Med Chem Lett. 2020 Apr 15;30(8):127051. doi: 10.1016/j.bmcl.2020.127051. Epub 2020 Feb 19.
A series of 3-nitro-naphthalimides 1(1a-1h) were designed and synthesized as antitumor agents. MTT assay results showed that all these compounds exhibited obvious antiproliferative activity against SKOV3, HepG2, A549, T-24 and SMMC-7721 cancer cell lines, while compound 1a displayed the best antiproliferative activity against HepG2 and T-24 cell lines in comparison with mitonafide, with IC of 9.2 ± 1.8 and 4.133 ± 0.9 μM, respectively. In vivo antiproliferative activity assay results showed that compound 1a exhibited good antiproliferative activity in the HepG2 and T-24 models, compared with mitonafide. Action mechanism results showed that compound 1a could induced the damage of DNA and the inhibition topo I, accompanying by inducing the G2-stage arresting and the apoptosis of T-24 cancer cells through up-regulating expression levels of cyclin B1, cdc 2-pTy, Wee1, γH2AX, p21, Bax and cytochrome c and down-regulating expression of Bcl-2.
一系列 3-硝基-萘酰亚胺 1（1a-1h）被设计并合成作为抗肿瘤剂。MTT 检测结果表明，所有这些化合物对 SKOV3、HepG2、A549、T-24 和 SMMC-7721 癌细胞系均表现出明显的增殖抑制活性，而与米托萘酚相比，化合物 1a 对 HepG2 和 T-24 细胞系表现出最佳的增殖抑制活性，其 IC 分别为 9.2±1.8 和 4.133±0.9 μM。体内增殖抑制活性检测结果表明，与米托萘酚相比，化合物 1a 在 HepG2 和 T-24 模型中表现出良好的增殖抑制活性。作用机制结果表明，化合物 1a 可通过诱导 DNA 损伤和拓扑异构酶 I 抑制，同时通过上调细胞周期蛋白 B1、cdc 2-pTy、Wee1、γH2AX、p21、Bax 和细胞色素 c 的表达水平，下调 Bcl-2 的表达，诱导 T-24 癌细胞的 G2 期阻滞和凋亡。
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