The interaction of aminoacridines with nucleic acids

Peacocke, A. R.; Skerrett, J. N. H.

doi:10.1039/tf9565200261

Cited by 546 publications

(185 citation statements)

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“…Values for r and c were calculated according to the treatment of Peacocke and Skerrett. 29) The linear fitting of r vs. r/c was carried out using a KaleidaGraph version 3.0. To a buffered aqueous solution (10 mM sodium phosphate and 100 mM sodium chloride, pH 7.0) of CTDNA (about 30 mM) was added aliquots of the TMPyP or hybrid solution, and CD spectra in the UV range were recorded.…”

Section: -(4-methoxycarbonylphenyl)-101520-tris(4-pyridyl)porphinementioning

confidence: 99%

Efficient Photocleavage of DNA by Cationic Porphyrin. Acridine Hybrids with the Effective Length of Diamino Alkyl Linkage.

Ishikawa

Yamashita

Uno

2001

CHEMICAL & PHARMACEUTICAL BULLETIN

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The development of compounds which modify nucleic acid structure is a current research area and can make a significant contribution to anti-tumor and -viral chemotherapy.1,2) For example, drugs like bleomycin (BLM) [3][4][5] capable of binding to and cleaving nucleic acids are expected to suppress the proliferation of malignant cells by blocking the flow of genetic information. From this point of view, cationic meso-tetrakis(4-N-methylpyridiniumyl)porphine (TMPyP) has been carefully studied and noted for its bifunctionality: i) the tight interaction with DNA through the three types of binding mode including intercalation, outside binding in the groove, and outside binding with self-stacking along the DNA surface, 6,7) and ii) the marked photochemical nuclease activity.8-10) Such a positively charged photosensitizer 11,12) would also be useful in the photodynamic therapy of cancer. 13,14) Some hybrid molecules composed of a non-charged porphyrin and acridines have been synthesized as a functional BLM model. [15][16][17] Acridine is known as an intercalator, 18,19) and hence the metal complexes of the hybrids bind to DNA via the acridine moiety, and then cause strand breaks by generating reactive oxygen species in the presence of reducing or oxidizing agents. To achieve higher and more efficient chemical modification of negatively charged DNA, we have for the first time synthesized positively charged porphyrin-acridine hybrids, 1-4, which are linked with various lengths of a diamino alkyl chain. In this paper we report their photo-nuclease activity and interaction with DNA. Our data show that they exhibit more enhanced photo-induced nuclease activity than TMPyP, and suggest that acridine and porphyrin moiety in the hybrids interact with DNA by the intercalative and outside groove binding, respectively. Results and DiscussionSynthesis of the Cationic Porphyrin-Acridine HybridsThe synthetic procedures for the positively charged porphyrin-acridine hybrids 1-4 are illustrated in Chart 1. One equivalent of terephthalaldehydic acid methyl ester, 3 eq of pyridine-4-aldehyde, and 4 eq of pyrrole were reacted in propionic acid for 1.5 h. The resultant mixture including six porphyrin isomers was separated on silica gel. The fifth eluted isomer, 5-(4-methoxycarbonylphenyl)-10,15,20-tris(4-pyridyl)-porphine, 9, obtained in 5.9% yield was then hydrolyzed with lithium hydroxide to give 5-(4-carboxyphenyl)-10,15,20-tris(4-pyridyl)porphine, 10, almost quantitatively. Condensation of 1 eq of 10 with 5-7 eq of acridine-diaminoalkane derivatives, 20) 5-8, using 5-7 eq of carbonyldiimidazole (CDI) in an absolute 50/50 (v/v) DMF-DMSO solution afforded corresponding porphyrin-acridine hybrids, 11-14, in 22-46% yield. The products were then methylated with excess methyl iodide in DMF for 3 h to give the final products, 1-4, quantitatively. Characterization of the compounds was accomplished using 1 H-NMR spectroscopy, matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS), and elemental analysis.Photo...

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Section: -(4-methoxycarbonylphenyl)-101520-tris(4-pyridyl)porphinementioning

confidence: 99%

Efficient Photocleavage of DNA by Cationic Porphyrin. Acridine Hybrids with the Effective Length of Diamino Alkyl Linkage.

Ishikawa

Yamashita

Uno

2001

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…The analysis of the binding mechanisms has been the object of studies for many years [4][5][6][7][8][9][10][11][12][13] and it is believed that the mechanism can be described by the intercalation model [6].…”

Section: Introductionmentioning

confidence: 99%

Binding and arrangement of non‐histone proteins in chromatin‐like structures from mammalian cells

Jost

Clark

1975

FEBS Letters

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“…The aminoacridine group enables the molecule to intercalate with DNA (Karle, Cysk & Karle, 1980;Lerman, 1961;Nandi, Debnath & Maiti, 1990;Reddy, Seshadri, Sakore & Sobell, 1979;Peacocke & ( (Cremer & Pople, 1975) Ring…”

Section: Commentmentioning

confidence: 99%

9-Methyl-10-(4-methylphenyl)-3,4,6,7,9,10-hexahydro-1,8(2H,5H)-acridinedione

Sivaraman¹,

Subramanian²,

Velmurugan³

et al. 1994

Acta Crystallogr C

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The title molecule, C21H23NO2, includes a partially hydrogenated acridine ring system. The central ring adopts a conformation which is predominantly boat in form (Acs = 2 °) while the two outer six-membered rings have approximate chair and twist-boat conformations (AcE = 2.6 and 8.6°), respectively. The molecule has approximate mirror symmetry with the phenyl ring in the non-crystallographic mirror plane. There is considerable folding along the bonds at the ring junctions. The packing of molecules involves van der Waals interactions. 06

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The interaction of aminoacridines with nucleic acids

Cited by 546 publications

References 2 publications

Efficient Photocleavage of DNA by Cationic Porphyrin. Acridine Hybrids with the Effective Length of Diamino Alkyl Linkage.

Efficient Photocleavage of DNA by Cationic Porphyrin. Acridine Hybrids with the Effective Length of Diamino Alkyl Linkage.

Binding and arrangement of non‐histone proteins in chromatin‐like structures from mammalian cells

9-Methyl-10-(4-methylphenyl)-3,4,6,7,9,10-hexahydro-1,8(2H,5H)-acridinedione

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