Synthetic models related to DNA intercalating molecules: Preparation of 9‐aminoacridines linked to the nucleotide bases adenine, guanine and thymine

Constant, Jean‐François; Carden, Brian M.; Lhomme, Jean

doi:10.1002/jhet.5570220422

Cited by 9 publications

(3 citation statements)

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“…Materials. The following compounds have been prepared and described before: Ade-C3 (6), Thy-C3 (7), and Gua-C3 (8) (Brown et al, 1968;Leonard et al, 1969); Ade-C3-Acr (2a), Thy-C3-Acr (3a), and Acr-C3 (5) (Bolte et al, 1982); Ade-C5-Acr (2b), Ade-C6-Acr (2c), Thy-C5-Acr (3b), Thy-C6-Acr (3c), Gua-Cs-Acr (4b), and Gua-C6-Acr (4c) (Constant et al, 1985). All compounds were tested for purity by a variety of methods including microanalysis, 'H NMR spectroscopy, thin-layer chromatography, and high-performance liquid chromatography (HPLC) in different solvent systems.…”

Section: Methodsmentioning

confidence: 99%

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Heterodimeric molecules including nucleic acid bases and 9-aminoacridine. Spectroscopic studies, conformations, and interactions with DNA

Constant

Laugâa²,

Roques³

et al. 1988

Biochemistry

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Heterodimeric molecules have been examined in which the 9-amino-6-chloro-2-methoxyacridine ring is linked to the nucleic acid bases adenine, thymine, and guanine by polymethylenic chains (CH2)n of varying length (n = 3, 5, 6). A detailed analysis has been performed, including hypochromism measurement in the UV, chemical shift variations in Fourier transform proton magnetic resonance, and fluorescence emission. All these techniques show that all molecules exist mainly under folded conformations in water in the temperature range 0-90 degrees C, with the acridine and the base rings being stacked one on top of the other. The thermodynamic parameters for the folded in equilibrium unfolded conformational equilibrium were estimated. The geometry of the intramolecular complexes could be determined. (1) All these data give information on the strength and nature of the base-acridine interactions as a function of different parameters such as solvent, temperature, etc. (2) The molecules under study constitute "spectroscopic models" for the drug-base complexes as they occur in DNA. In particular, we show the dramatic influence of the relative orientations of the two stacked chromophores in the complex upon the magnitude of % H, the percent hypochromism. The quenching and enhancement of acridine fluorescence emission induced respectively by guanine and adenine is evidenced and quantitatively estimated. (3) These base-acridine heterodimers bind to DNA to an extent that is inversely proportional to their degree of intramolecular stacking.

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Section: Methodsmentioning

confidence: 99%

“…stacking interactions in binding processes. From this observation we have prepared (Constant et al, 1985) new molecules, which are described in this paper (Chart I). These compounds attach the three bases adenine (2b,c), thymine (3b,c), and guanine (4b,c) to a quinacrine ring by either a C5 or C6 chain.…”

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confidence: 99%

Heterodimeric molecules including nucleic acid bases and 9-aminoacridine. Spectroscopic studies, conformations, and interactions with DNA

Constant

Laugâa²,

Roques³

et al. 1988

Biochemistry

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“…The following compounds have been prepared as previously described Ade-C3-Acr (16), Acr-Z (17), Ade-C5-Acr and Ade-C6-Acr (18). The synthesis of Ade-Z and Ade-Z-Acr will be descri bed elsewhere.…”

Section: Preparation Of Organic Moleculesmentioning

confidence: 99%

9-[(10-(aden-9-yl)-4,8-diazadecyl)amino]-6-chloro-2-methoxy-acridine incises DNA at apurinic sites

Constant

O’Connor

Lhomme³

et al. 1988

Nucl Acids Res

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The incision of DNA at apurinic/apyrimidinic sites (AP-sites) by chloro-6-methoxy-2 [(adenyl-9)-11)-4,8 diazadecyl]amino-9 acridine (Ade-Z-Acr), a 9-aminoacridine linked to an adenine, at nanomolar concentrations is described. Moreover, this drug, Ade-Z-Acr, is one of the most efficient drugs which cleaves DNA at AP-sites. The high activity is the result of the composition of the drug, since the individual components have no incising activity in the concentration range studied. The termini left by the Ade-Z-Acr molecule are a 3'deoxyribose and a 5'nucleotide. The termini and the inability of the Ade-Z-Acr to incise DNA with reduced AP-sites suggest that the mechanism of cleavage is beta-elimination.

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New Arylpiperazines with Flexible versus Partly Constrained Linker as Serotonin 5‐HT_1A/5‐HT₇ Receptor Ligands

Kowalski

Mitka

Jaśkowska

et al. 2013

Archiv der Pharmazie

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A series of new long-chain arylpiperazine (LCAP) derivatives with flexible and partly constrained alkyl linker were synthesized and investigated in vitro as potential serotonin 5-HT(1A) and 5-HT(7) receptor ligands. The compounds were prepared by a two-step procedure using naphthalimide and 2H-1,3-benzoxazine-2,4(3H)-dione as imides, and 1-(2-methoxyphenyl)piperazine (o-OMe-PhP) and 1,2,3,4-tetrahydroisoquinoline (THIQ) as amine pharmacophores. Modifications of the spacer structure included introduction of flexible penta- and hexamethylene chains as well as partly constrained m- and p-xylyl moieties. In general, the new compounds were more active at the 5-HT(1A) than at the 5-HT(7) receptor, and the o-OMe-PhP derivatives displayed higher affinities than their respective THIQ analogs. The spacer modifications had little effect on the observed in vitro activities. Within the o-OMe-PhP series, except for a small binding reduction for ligands containing the m-xylyl moiety, there was no substantial change in the compounds' potency at both receptors, while for the THIQ derivatives a clear structure-activity relationship was visible only for the interaction of the compounds with the 5-HT(7) receptor, which strongly favored flexible analogs.

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Synthetic models related to DNA intercalating molecules: Preparation of 9‐aminoacridines linked to the nucleotide bases adenine, guanine and thymine

Abstract: A series of novel compounds were prepared in which the aromatic ring of the drug quinacrine (2‐methoxy‐6‐chloro‐9‐alkylaminoacridine) is linked to the nucleotide bases adenine, guanine and thymine by penta‐and hexamethylene bridges.

Cited by 9 publications

References 18 publications

Heterodimeric molecules including nucleic acid bases and 9-aminoacridine. Spectroscopic studies, conformations, and interactions with DNA

Heterodimeric molecules including nucleic acid bases and 9-aminoacridine. Spectroscopic studies, conformations, and interactions with DNA

9-[(10-(aden-9-yl)-4,8-diazadecyl)amino]-6-chloro-2-methoxy-acridine incises DNA at apurinic sites

New Arylpiperazines with Flexible versus Partly Constrained Linker as Serotonin 5‐HT_1A/5‐HT₇ Receptor Ligands

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Synthetic models related to DNA intercalating molecules: Preparation of 9‐aminoacridines linked to the nucleotide bases adenine, guanine and thymine

Abstract: A series of novel compounds were prepared in which the aromatic ring of the drug quinacrine (2‐methoxy‐6‐chloro‐9‐alkylaminoacridine) is linked to the nucleotide bases adenine, guanine and thymine by penta‐and hexamethylene bridges.

Cited by 9 publications

References 18 publications

Heterodimeric molecules including nucleic acid bases and 9-aminoacridine. Spectroscopic studies, conformations, and interactions with DNA

Heterodimeric molecules including nucleic acid bases and 9-aminoacridine. Spectroscopic studies, conformations, and interactions with DNA

9-[(10-(aden-9-yl)-4,8-diazadecyl)amino]-6-chloro-2-methoxy-acridine incises DNA at apurinic sites

New Arylpiperazines with Flexible versus Partly Constrained Linker as Serotonin 5‐HT1A/5‐HT7 Receptor Ligands

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Product

Resources

About

New Arylpiperazines with Flexible versus Partly Constrained Linker as Serotonin 5‐HT_1A/5‐HT₇ Receptor Ligands