54824-17-8

Usage

Uses

A Naphthalimides with potent anticancer activity.

InChI:InChI=1/C16H15N3O4/c1-17(2)6-7-18-15(20)12-5-3-4-10-8-11(19(22)23)9-13(14(10)12)16(18)21/h3-5,8-9H,6-7H2,1-2H3

Upstream product

• 3027-38-1 3-nitro-1,8-naphthalic anhydride 
• 108-00-9 N,N-dimethylethylenediamine 
• 81-84-5 1,8-Naphthalic anhydride 

Downstream Products

• 69408-81-7 amonafide 
• 1098129-38-4 5-(3'-nitro-phenyl)-2-[2-(dimethylamino)ethyl]-1H-benzo[de]isoquinoline-1,3(2H)-dione 
• 69409-02-5 2-[2-(dimethylamino)ethyl]-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinoline-5-ylacetamide 
• 868962-59-8 5-{[(2-(2-phenoxy)-6-hydroxymethyltetrahydropyran-3,4,5-triol)-5-ylmethyl]amino}-N-(2-[2-(dimethylamino)ethyl]-1H-benzo[de]isoquinolin-1,3(2H)-dione) 
• 937261-90-0 C₃₅H₃₉N₃O₁₁ 
• 868962-66-7 5-{[(1Z)-benzo-(3,5-bis(acetoxy)-2-[(acetoxy)methyl]-6-oxy-tetrahydro-2H-pyran-4-ylacetate)-5-ylmethylene]amino}-N-(2-[2-(dimethylamino)ethyl]-1H-benzo[de]isoquinolin-1,3(2H)-dione) 
• 868962-44-1 2-[2-(dimethylamino)ethyl]-5-{[(1Z)-(2,5-dihydroxyphenyl)methylene]amino}-1H-benzo[de]isoquinoline-1,3(2H)-dione 

Relevant academic research and scientific papers

Real-Time Multi-Photon Tracking and Bioimaging of Glycosylated Theranostic Prodrugs upon Specific Enzyme Triggered Release

Real-time tracking of prodrug uptake, delivery and activation in vivo represents a major challenge for prodrug development. Herein, we demonstrate the use of novel glycosylated theranostics of the cancer pharmacophore Amonafide in highly-selective, enzyma

1,8-naphthalimide derivative having selective inhibition effect on non-small cell lung cancer, and synthesis method and application thereof

The invention discloses a 1,8-naphthalimide derivative having a selective inhibition effect on non-small cell lung cancer, and a synthesis method and an application thereof. The synthesis method of the 1,8-naphthalimide derivative comprises the following steps: taking and dissolving amonafide and 4-fluorobenzoyl chloride in an organic solvent, performing a reaction, and removing the solvent afterthe reaction ends in order to obtain a crude target product. Test of the applicant in the invention shows that the derivative has significant biological activity, especially has significant biologicalactivity to a non-small cell lung cancer cell line HCC-827 and other tumor cell lines, has few toxic and side effects on normal human cells, and is expected to be developed into targeted therapeuticdrugs. The structure of the 1,8-naphthalimide derivative is represented by formula (I) shown in the description.

Cytotoxic activity and DNA binding of naphthalimide derivatives with amino acid and dichloroacetamide functionalizations

A series of novel naphthalimide derivatives modified by amino acids and their dichloroacetamide derivatives at the 3-position have been synthesized. Their cytotoxic activities were preliminarily evaluated against Hela, A549 and K562 cells, which showed that the length of the side chains of the amino acids influenced the cytotoxic activities. Moreover, compound 7d showed a very good cytotoxic activity against A549 cells with an IC50 value of 4.78 μmol L-1. Furthermore, the UV-vis, fluorescence, and circular dichroism (CD) spectroscopies and thermal denaturation experiment indicated that compounds 6a, 6d and 7a, 7d, as DNA intercalators, exhibited binding affinities with calf-thymus DNA (Ct-DNA).

A novel hydrazino-substituted naphthalimide-based fluorogenic probe for tert-butoxy radicals

A novel fluorogenic probe for tert-butoxy radicals based on the hydrazino-naphthalimide system is reported. Interestingly, different regioisomers exhibited significantly different optical properties toward ROS, which suggested 4-hydrazinyl naphthalimide as a potential new platform for the in vitro and in cellulo detection of alkoxyl radicals.

A novel hydrazino-substituted naphthalimide-based fluorogenic probe for tert-butoxy radicals

A novel fluorogenic probe for tert-butoxy radicals based on the hydrazino-naphthalimide system is reported. Interestingly, different regioisomers exhibited significantly different optical properties toward ROS, which suggested 4-hydrazinyl naphthalimide as a potential new platform for the in vitro and in cellulo detection of alkoxyl radicals.

Synthesis and study of antiproliferative, antitopoisomerase II, DNA-intercalating and DNA-damaging activities of arylnaphthalimides

A series of arylnaphthalimides were designed and synthesized to overcome the dose-limiting cytotoxicity of N-acetylated metabolites arising from amonafide, the prototypical antitumour naphthalimide whose biomedical properties have been related to its ability to intercalate the DNA and poison the enzyme Topoisomerase II. Thus, these arylnaphthalimides were first evaluated for their antiproliferative activity against two tumour cell lines and for their antitopoisomerase II in vitro activities, together with their ability to intercalate the DNA in vitro and also through docking modelization. Then, the well-known DNA damage response in Saccharomyces cerevisiae was employed to critically evaluate whether these novel compounds can damage the DNA in vivo. By performing all these assays we conclude that the 5-arylsubstituted naphthalimides not only keep but also improve amonafide's biological activities.

Fluorescence properties and antiproliferative effects of mono-, bis-, and tris- thiophenylnaphthalimides: Results of a comparative pilot study

A series of mono-, bis- and trisnaphthalimides with different substituents on the naphthalimide ring system was prepared. For compounds containing a thiophenyl substituent fluorescence spectroscopic measurements were performed and unexpectedly showed an increase in fluorescence emission for the bis- and trisnaphthalimide derivatives in phosphate buffered saline. Additional fluorescence microscopic experiments indicated an efficient cellular uptake of the thiophenyl substituted compound 1c into cultured tumor cells. Experiments on the inhibition of tumor cell proliferation were performed in MCF-7 breast adenocarcinoma and HT-29 colon carcinoma cells and confirmed derivatives containing a nitro substituent as the most active compounds. Compound 1c demonstrated potential as photoinducable antitumor agent.

Small molecule modifiers of MicroRNA miR-122 function for the treatment of hepatitis C Virus infection and hepatocellular carcinoma

MicroRNAs are a recently discovered new class of important endogenous regulators of gene function. Aberrant regulation of microRNAs has been linked to various human diseases, most importantly cancer. Small molecule intervention of microRNA misregulation h

2,2,2-Trichloro-N-({2-[2-(dimethylamino)ethyl]-1,3-dioxo-2, 3-dihydro-1H-benzo[de]isoquinolin-5-yl}carbamoyl)acetamide (UNBS3157), a novel nonhematotoxic naphthalimide derivative with potent antitumor activity

Amonafide (1), a naphthalimide which binds to DNA by intercalation and poisons topoisomerase IIα, has demonstrated activity in phase II breast cancer trials, but has failed thus far to enter clinical phase III because of dose-limiting bone marrow toxicity. Compound 17 (one of 41 new compounds synthesized) is a novel anticancer naphthalimide with a distinct mechanism of action, notably inducing autophagy and senescence in cancer cells. Compound 17 (2,2,2-trichloro-N-({2-[2-(dimethylamino)ethyl]-1,3-dioxo-2,3-dihydro-1H- benzo[de]isoquinolin-5-yl}carbamoyl)acetamide (UNBS3157)) was found to have a 3-4-fold higher maximum tolerated dose compared to amonafide and not to provoke hematotoxicity in mice at doses that display significant antitumor effects. Furthermore, 17 has shown itself to be superior to amonafide in vivo in models of (i) L1210 murine leukemia, (ii) MXT-HI murine mammary adenocarcinoma, and (iii) orthotopic models of human A549 NSCLC and BxPC3 pancreatic cancer. Compound 17, therefore, merits further investigation as a potential anticancer agent.

NAPHTHALIMIDE SYNTHESIS INCLUDING AMONAFIDE SYNTHESIS AND PHARMACEUTICAL PREPARATIONS THEREOF

The present invention concerns novel methods for the synthesis of naphthalimides and mitonafide analogs, as well as salts thereof. Also included are novel compositions, including naphthalimides and naphthalimide salts, analogs thereof, as well as stable liquid dosage forms thereof.