23204-38-8Relevant articles and documents
Thiazonaphthalimide derivatives: Synthesis and interaction with DNA
Botz, Alexandra,Chenavier, Yves,Pécaut, Jacques,Delangle, Pascale,Gateau, Christelle
, p. 2550 - 2553 (2018)
The synthesis of several thiazonaphthalimide derivatives is described. The exclusive formation of angular rather than linear isomers was unequivocally demonstrated by NMR and single crystal X-ray diffraction. Their photophysical properties and ability to bind calf-Thymus DNA with affinities in the range of 104 makes them interesting candidates to probe DNA by fluorescence.
A potent aminonaphthalimide platinum(IV) complex with effective antitumor activities in vitro and in vivo displaying dual DNA damage effects on tumor cells
Wang, Qingpeng,Chen, Yan,Li, Guoshuai,Zhao, Yanna,Liu, Zhifang,Zhang, Ruiyan,Liu, Min,Li, Dacheng,Han, Jun
, (2019)
A new aminonaphthalimide platinum(IV) complex was developed by incorporating aminonaphthalimide, a DNA intercalator, into the platinum(IV) system. This complex displayed potent antitumor activities against all tested tumor cell lines in vitro and showed great potential in overcoming drug resistance of cisplatin. Moreover, it remarkably inhibited the growth of CT26 xenografts in BALB/c mice without severe side effects in vivo. Then, the compound exhibited a dual DNA damage antitumor mechanism that it could interact with DNA in tetravalent form via the naphthalimide group to cause DNA lesion, and the further liberation of platinum(II) complex after reduction would induce remarkable secondary damage to DNA. Meanwhile, it caused cell apoptosis through an intrinsic apoptosis pathway by up-regulating the expression of caspase 3 and caspase 9.
Design, antiviral and cytostatic properties of isoxazolidine-containing amonafide analogues
Kokosza, Kamil,Andrei, Graciela,Schols, Dominique,Snoeck, Robert,Piotrowska, Dorota G.
, p. 3135 - 3146 (2015)
Abstract A novel series of 5-arylcarbamoyl- and 5-arylmethyl-2-methylisoxazolidin-3-yl-3-phosphonates have been synthesized via cycloaddition of N-methyl-C-(diethoxyphosphoryl)nitrone with N-substituted naphthalimide acrylamides and N-allylnaphthalimides. All cis- and trans-isoxazolidine phosphonates obtained herein were assessed for antiviral activity against a broad range of DNA and RNA viruses. Isoxazolidines trans-9d and trans-9f exhibited the highest activity (EC50 = 8.9 μM) toward cytomegalovirus. Compounds cis- and trans-9d as well as cis- and trans-9f were found potent against HSV and Vaccinia viruses (EC50 in the 45-58 μM range), whereas isoxazolidines 10a and 10d suppressed replication of Coxsackie B4 and Punta Toro viruses (EC50 in the 45-73 μM range). Antiproliferative evaluation of all obtained isoxazolidines revealed the promising activity of cis-9b, cis-9d, trans-9d, cis-9e, trans-9e, cis-9f and trans-9f toward tested cancer cell lines with IC50 in the 1.1-19 μM range.
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)
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.
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.
Naphthalimide indole heterocyclic compound as well as preparation method and application thereof
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, (2021/06/06)
The invention belongs to the technical field of medicinal chemistry, and particularly relates to a naphthalimide indole heterocyclic compound as well as a preparation method and application thereof. The naphthalimide indole heterocyclic compound has good anti-tumor activity, the in-vivo and in-vitro anti-tumor activity of the naphthalimide indole heterocyclic compound is better than that of dinafide, and the anti-tumor spectrum of the naphthalimide indole heterocyclic compound is wide. Different from classical dinafide, the compound regulates and controls subcellular organelle and cell nucleus functions to reverse drug resistance by targeting the contents of key enzyme PAO (polyamine oxidase) and three endogenous small molecules Put (putrescine), Spd (spermidine) and Spm (spermine) in a tumor polyamine microenvironment, and enhances anti-tumor immune response at the same time; and the compound has good treatment potential on advanced metastatic tumors. The complex provided by the invention also solves the problems of poor solubility, complicated clinical compatibility, poor patient immunity in clinical application of chemotherapeutic drugs and the like of naphthalimide analogues represented by dinafide in the prior art, and has good water solubility.
