3027-38-1Relevant articles and documents
Design, synthesis and biological evaluation of 3-nitro-1,8-naphthalimides as potential antitumor agents
Liang, Gui-Bin,Ma, Xian-Li,Su, Dan,Wei, Jian-Hua,Xin, Mao,Yang, Chen-Hui,Zhang, Ye
, (2020)
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 IC50 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.
Naphthalimide-polyamine conjugate as well as preparation method and application thereof
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, (2021/02/10)
The invention discloses a naphthalimide-polyamine conjugate, which has a structural general formula as shown in I, a novel skeleton, high efficiency, low toxicity and good inhibitory activity for tumor cells. The invention also discloses a preparation method of the conjugate. Firstly, 3-amino groups with toxic and side effects of amonafide are removed, a phenylpyrazole structure fragment is introduced to the naphthalimide parent naphthalene ring, and a naphthalimide side chain with a polyamine chain is modified, acetyltransferase in vivo is prevented from acetylating the amino groups on the naphthalene ring of amonafideand, and toxic and side effects are reduced; and further by introducing a low-toxicity phenyl pyrazole active structure fragment, the naphthalimide polyamine conjugate witha novel skeleton, high efficiency and low toxicity is synthesized; and secondly, quinazoline with low toxicity is introduced to replace hydrogen atoms of amonafide 3-amino, so that the naphthalimide polyamine conjugate with anti-tumor activity and low toxicity is obtained. The invention also discloses an application of the conjugate in preparation of antitumor drugs, and good development potentialis realized.
A naphthalimide-polyamine conjugate preferentially accumulates in hepatic carcinoma metastases as a lysosome-targeted antimetastatic agent
Ma, Jing,Li, Linrong,Yue, Kexin,Zhang, Zhansheng,Su, Shihao,Chen, Yutong,Yu, Lu,Zhang, Pengfei,Ma, Ruijuan,Li, Yingguang,Ma, Yinxia,Jia, Huinan,Wang, Chaojie,Wang, Jiajia,Xie, Songqiang
, (2021/05/10)
Disseminated tumors lead to approximately 90% of cancer-associated deaths especially for hepatocellular carcinoma (HCC), indicating the imperative need of antimetastatic drugs and the ineffectiveness of current therapies. Recently polyamine derivatives have been identified as a promising prospect in dealing with metastatic tumors. Herein, a novel class of naphthalimide-polyamine conjugates 8a-8d, 13a-13c, 17 and 21 were synthesized and the mechanism was further determined. The polyamine conjugate 13b displayed remarkably elevated anti-tumor and anti-metastatic effects (76.01% and 75.02%) than the positive control amonafide (46.91% and 55.77%) at 5 mg/kg in vivo. The underlying molecular mechanism indicated that in addition to induce DNA damage by up-regulating p53 and γH2AX, 13b also targeted lysosome to modulate polyamine metabolism and function in a totally different way from that of amonafide. Furthermore, the HMGB1/p62/LC3II/LC3I and p53/SSAT/β-catenin pathways were mainly involved in the inhibition of 13b-induced HCC metastasis by targeting polyamine transporters (PTs) overexpressed in HCC. At last, 13b down-regulated the concentrations of Put, Spd and Spm by modulating polyamine metabolism key enzymes SSAT and PAO, which favored the suppression of fast growing tumor cells. Taken together, our study implies a promising strategy for naphthalimide conjugates to treat terminal cancer of HCC by targeting autophagy and tumor microenvironment with reduced toxicities and notable activities.
Fluorescent probe for detecting tiredness level Preparation method and application thereof
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Paragraph 0044-0049, (2021/09/08)
The invention discloses a fluorescence probe for detecting the level of hypoxia, a preparation method and application thereof, and can realize specific response Na. 2 S2 O4 The fluorescence probe is used for detecting the tiredness level, and the structure is as follows. The probe comprises a nitrogen-nitrogen double bond, which can be broken down in a hypoxic environment to cause fluorescence recovery of the compound. The naphthalimide is introduced as a fluorophore, and has the characteristics of stable fluorescence and high fluorescence quantum efficiency. The fluorescent probe is simple and convenient to prepare, obvious in spectral change, good in specificity effect, small in cytotoxicity, good in imaging effect and good in specificity detection Na. 2 S2 O4 , The fluorophore precursor and the anti-tumor drug nitrogen mustard compound can be released under the hypoxic condition, the tumor cell growth can be inhibited while the hypoxia imaging is carried out, the diagnosis and treatment integrated function is achieved, and the application prospect is good.
