School of Pharmacy, Guilin Medical University, Guilin 541004, China.
School of Pharmacy, Guilin Medical University, Guilin 541004, China.
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。
