69408-81-7

Usage

Uses

Used in Oncology:
Amonafide is used as an antineoplastic agent for the treatment of neoplastic diseases. It works by intercalating into DNA and inhibiting topoisomerase II, which leads to the prevention of DNA replication and transcription, ultimately resulting in the death of cancer cells.
Used in Cancer Therapy:
Amonafide is used as a therapeutic agent in cancer treatment. Its mechanism of action involves the intercalation into DNA and inhibition of topoisomerase II, which disrupts the essential processes of DNA replication and transcription in cancer cells, thereby exerting an antineoplastic effect.

Biological Activity

amonafide is a novel topoisomerase ii inhibitor. topoisomerase ii plays critical roles including dna transcription, replication and chromosome segregation. though the biological functions of topoisomerase ii are important for insuring genomic integrity, the ability to interfere with topoisomerase ii and generate enzyme mediated dna damage is an effective strategy for cancer chemotherapy.

in vitro

amonafide intercalated with dna and disrupted the loading of topoisomerases. in contrast to the classic agents, amonafide was found to induce higher molecular weight fragmentation, resulting in the apoptosis without dna cleavage. amonafide was found to act in an atp-independent manner and seemed unlikely to induce the chromosome translocations associated with treatmentinduced leukemia [1].

in vivo

amonafide was found to be able to inhibit ip l1210 leukemia, with optimal increased life spans (ils) of 61% to 106% following single 16 mg/kg dosing on days 1 to 9. similar efficacy was noted against ip p388 murine leukemia and the sc implanted l1210 leukemia. additionally, amonafide demonstrated activity against two nonleukemic ip implanted murine tumors, the m5076 sarcoma and the b16 melanoma [2].

IC 50

4.67, 2.73, and 6.38 for ht-29, hela, and pc3 cells, respectively

references

[1] freeman cl,swords r,giles fj. amonafide: a future in treatment of resistant and secondary acute myeloid leukemia expert rev hematol.2012 feb;5(1):17-26. [2] saez r,craig jb,kuhn jg,weiss gr,koeller j,phillips j,havlin k,harman g,hardy j,melink tj, et al. phase i clinical investigation of amonafide. j clin oncol.1989 sep;7(9):1351-8.

InChI:InChI=1/C16H17N3O2/c1-18(2)6-7-19-15(20)12-5-3-4-10-8-11(17)9-13(14(10)12)16(19)21/h3-5,8-9H,6-7,17H2,1-2H3

Upstream product

• 23204-38-8 3-amino-naphthalene-1,8-dicarboxylic acid-anhydride 
• 108-00-9 N,N-dimethylethylenediamine 
• 54824-17-8 mitonafide 
• 81-84-5 1,8-Naphthalic anhydride 
• 3027-38-1 3-nitro-1,8-naphthalic anhydride 

Downstream Products

• 868962-44-1 2-[2-(dimethylamino)ethyl]-5-{[(1Z)-(2,5-dihydroxyphenyl)methylene]amino}-1H-benzo[de]isoquinoline-1,3(2H)-dione 
• 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) 
• 69409-02-5 2-[2-(dimethylamino)ethyl]-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinoline-5-ylacetamide 
• 937261-90-0 C₃₅H₃₉N₃O₁₁ 
• 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) 
• 1358552-78-9 2-[2-(dimethylamino)ethyl]-5-[(4-methoxylphenyl)amino]-1H-benzo[de]isoquinoline-1,3(2H)-dione 
• 1358552-81-4 2-[2-(dimethylamino)ethyl]-5-[(4-nitrophenyl)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

A naphthalimide-polyamine conjugate preferentially accumulates in hepatic carcinoma metastases as a lysosome-targeted antimetastatic agent

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

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.

Design, synthesis, and evaluation of novel 3-carboranyl-1,8-naphthalimide derivatives as potential anticancer agents

We synthesized a series of novel 3-carboranyl-1,8-naphthalimide derivatives, mitonafide and pinafide analogs, using click chemistry, reductive amination and amidation reactions and investigated their in vitro effects on cytotoxicity, cell death, cell cycle, and the production of reactive oxygen species in a HepG2 cancer cell line. The analyses showed that modified naphthalic anhydrides and naphthalimides bearing ortho-or meta-carboranes exhibited diversified activity. Naphthalimides were more cytotoxic than naphthalic anhydrides, with the highest IC50 value determined for compound 9 (3.10 μM). These compounds were capable of inducing cell cycle arrest at G0/G1 or G2M phase and promoting apoptosis, autophagy or ferroptosis. The most promising conjugate 35 caused strong apoptosis and induced ROS production, which was proven by the increased level of 2′-deoxy-8-oxoguanosine in DNA. The tested conjugates were found to be weak topoisomerase II inhibitors and classical DNA intercalators. Compounds 33, 34, and 36 fluorescently stained lysosomes in HepG2 cells. Additionally, we performed a similarity-based assessment of the property profile of the conjugates using the principal component analysis. The creation of an inhibitory profile and descriptor-based plane allowed forming a structure–activity landscape. Finally, a ligand-based comparative molecular field analysis was carried out to specify the (un)favorable structural modifications (pharmacophoric pattern) that are potentially important for the quantitative structure– activity relationship modeling of the carborane–naphthalimide conjugates.

Hydrogen sulfide triggered molecular agent for imaging and cancer therapy

We developed an activatable molecular reagent, PNF, triggered by intracellular H2S in the lysosome to release the therapeutic drug amonafide, which can escape from the lysosome into the nucleus to induce autophagy of cancer cells. PNF exhibits potent inhibitory activity against cisplatin-resistant tumor cell lines.

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.

Low-toxicity 1,8-naphthalimide derivative and synthetic method and application thereof

The invention discloses a low-toxicity 1,8-naphthalimide derivative and a synthetic method and application thereof. The synthetic method of the 1,8-naphthalimide derivative mainly comprises the following steps: dissolving amonafide and 2-fluorobenzoyl chloride in an organic solvent and reacting; and after reaction is finished, removing a solvent to obtain a coarse product as a target object. Testsshow that the derivative has remarkable bioactivity, and particularly has remarkable inhibition activity to non-small cell lung cancer cell strains HCC-827 and other tumor cell strains, moreover, toxic and side effects of human normal cells are small, and thus, the 1,8-naphthalimide derivative is expected to be developed into a targeted therapy drug. The structure of the 1,8-naphthalimide derivative is as shown in a formula (I) as shown in the specification.

Cancer cell-targeted two-photon fluorescence probe for the real-time ratiometric imaging of DNA damage

Real-time imaging of DNA damage in cancer cells could provide valuable information on the formation and development of cancer. Herein, a two-photon fluorescence probe was discovered. Through sequential ICT processes, it allows successful in vivo visualization of DNA damage in cancer cells by one/two-photon microscopic imaging or by the unaided eye and a hand-held ultraviolet lamp.

Design, antiviral and cytostatic properties of isoxazolidine-containing amonafide analogues

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.

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).