ChemInform Abstract: Synthesis, Structure and Antitumor Activity of New Benz(d,e) isoquinoline‐1,3‐diones

Braña, Miguel F.; Castellano, José María; Morán, Marina; Emling, F; Kluge, Michael; Schlick, E.; Klebe, Gehard; Walker, Nigel

doi:10.1002/chin.199615170

Cited by 6 publications

(7 citation statements)

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“…As is lucidly presented and discussed by Janiak, the laterally displaced ring systems seen in 4 would permit optimal π–σ attraction between stacked isoquinoline groups in addition to normal London forces of attraction. Isoquinoline and quinoline ring systems are, of course, well-known for their π-stacking ability and are often key pharmacophores prevalent in many anticancer, − antiviral, and antitrypanosome compounds with a mechanism of action (MOA) involving DNA binding by intercalation . Of special relevance to the present work, we note that the clinically deployed anticancer drug camptothecin (CPT; a quinoline alkaloid) poisons human Top1 by DNA intercalation at a 5′-TA-3′ dinucleotide site targeted for covalent binding by the enzyme during its catalytic cycle .…”

Section: Resultsmentioning

confidence: 94%

Gold(III) Complexes of Pyridyl- and Isoquinolylamido Ligands: Structural, Spectroscopic, and Biological Studies of a New Class of Dual Topoisomerase I and II Inhibitors

et al. 2013

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The structures, spectroscopy, and cytotoxicity of four novel nominally square-planar gold(III) chelates 1-4 with the general formula cis-AuCl2(X), where the ligand X is an anionic bidentate pyridyl- or isoquinolylamido chelating agent, are described. The Au-N(amido), Au-N(pyridyl), and Au-N(isoquinolyl) distances are 2.002(9)-2.016(3), 2.01(1)-2.037(3), and 2.037(3) Å, respectively. Density functional theory simulations afforded accurate gold(III) coordination geometries for 1-4 (bond distances and angles to within 5% of the X-ray values), while accurate transition energies were limited to those calculated in the UV spectral region. The complexes had variable stability in dimethyl sulfoxide: compound 3 (relatively rigid) was indefinitely stable, compounds 1 and 2 (conformationally flexible) slowly demetalated over 30 days, and 4 (extensively aromatic) formed an insoluble precipitate after 10 days (72 h in an aqueous buffer). The isoquinolylamido derivative 4 was sufficiently cytotoxic in the NCI-60 screen to undergo full five-dose testing. Notably low GI50 (1.8, 2.3, and 3.2 μM) and IC50 (4.0, 9.8, and 15 μM) values were recorded for the OVCAR-3, IGROV1, and SW-620 cell lines, respectively. Hierarchical cluster analysis employing the National Cancer Institute (NCI) data for known anticancer drugs and 4 revealed that compound 4 is mechanistically identical with the topoisomerase IIα (Top2) poison zorubicin and statistically similar to the topoisomerase IB (Top1) poisons camptothecin and 9-methoxycamptothecin. The Top2-catalyzed decatenation reaction of kinetoplast DNA was studied as a function of the concentration of 4: the compound acts as an interfacial poison of Top2 at low concentrations (<1 μM) and a catalytic inhibitor of the enzyme above 5 μM. Gel mobility shift assays (plasmid DNA substrate) showed that the catalytic inhibition of Top2 likely correlates with DNA binding by 4 at concentrations >5 μM. Compound 4 is also a catalytic inhibitor of Top1 at higher concentrations, consistent with DNA binding by the complex.

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Section: Resultsmentioning

confidence: 94%

Gold(III) Complexes of Pyridyl- and Isoquinolylamido Ligands: Structural, Spectroscopic, and Biological Studies of a New Class of Dual Topoisomerase I and II Inhibitors

et al. 2013

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“…Subsequently, Braña and co-workers reported the development of a series of 3-amino-6-nitro-1,8-naphthalimide derivatives. 12 These compounds exhibited very high cytotoxicity compared to 1 and 2 against human CX-1 colon carcinoma and LX-1 lung carcinoma cell lines. However, the presence of alkyne substitution at the 3-and 4-positions of the naphthalene ring was found to decrease the cytotoxic activity of these compounds.…”

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confidence: 93%

Recent advances in the development of 1,8-naphthalimide based DNA targeting binders, anticancer and fluorescent cellular imaging agents

et al. 2013

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The development of functional 1,8-naphthalimide derivatives as DNA targeting, anticancer and cellular imaging agents is a fast growing area and has resulted in several such derivatives entering into clinical trials.This review gives an overview of the many discoveries and the progression of the use of 1,8-naphthalimides as such agents and their applications to date; focusing mainly on mono-, bis-naphthalimide based structures, and their various derivatives (e.g. amines, polyamine conjugates, heterocyclic, oligonucleotide and peptide based, and those based on metal complexes). Their cytotoxicity, mode of action and cell-selectivity are discussed and compared. The rich photophysical properties of the naphthalimides (which are highly dependent on the nature and the substitution pattern of the aryl ring) make them prime candidates as probes as the changes in spectroscopic properties such as absorption, dichroism, and fluorescence can all be used to monitor their binding to biomolecules. This also makes them useful species for monitoring their uptake and location within cells without the use of co-staining. The photochemical properties of the compounds have also been exploited, for example, for photocleavage of nucleic acids and for the destruction of tumour cells.

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“…Many NDCI chromophores, characterized by both strong absorption and good fluorescence yields were prepared and used as fluorescent agents [1], azo dyes [2], antitumor [3,4] and antiviral drugs [5]. The NDCI derivatives are also reagents and intermediates in the synthesis of rigid-chain heterocyclic polymers used for preparing various super strength materials possessing special properties (for examplenonlinear optical, photoconducting, electroconducting, etc.)…”

Section: Introductionmentioning

confidence: 99%

Polyamines. IV. Spectroscopic properties of N,N-bis-(1,8-naphthalenedicarboximidopropyl)-N-propylamine and supramolecular interactions in its crystals

Borowiak

Wolska

Brycki

et al. 2010

Journal of Molecular Structure

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ChemInform Abstract: Synthesis, Structure and Antitumor Activity of New Benz(d,e) isoquinoline‐1,3‐diones

Cited by 6 publications

References 0 publications

Gold(III) Complexes of Pyridyl- and Isoquinolylamido Ligands: Structural, Spectroscopic, and Biological Studies of a New Class of Dual Topoisomerase I and II Inhibitors

Gold(III) Complexes of Pyridyl- and Isoquinolylamido Ligands: Structural, Spectroscopic, and Biological Studies of a New Class of Dual Topoisomerase I and II Inhibitors

Recent advances in the development of 1,8-naphthalimide based DNA targeting binders, anticancer and fluorescent cellular imaging agents

Polyamines. IV. Spectroscopic properties of N,N-bis-(1,8-naphthalenedicarboximidopropyl)-N-propylamine and supramolecular interactions in its crystals

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