Design, synthesis, and DNA binding properties of bifunctional intercalators. Comparison of polymethylene and diphenyl ether chains connecting phenanthridine

Cory, Michael; McKee, David D.; Kagan, J.; Henry, David W.; Miller, Joseph A.

doi:10.1021/ja00294a054

Cited by 420 publications

(204 citation statements)

References 0 publications

Supporting

Mentioning

181

Contrasting

Unclassified

Order By: Relevance

“…ethidium bromide). 22,23 The viscosity results unambiguously show that Fe(2,4-DHsalophen)Cl bind with DNA by groove binding mode, these results are in agreement with optical absorption experiments.…”

Section: Viscosity Measurementssupporting

confidence: 82%

Study of Interaction of Native DNA with Iron(III)-(2,4-Dihydroxysalophen)chloride

Azani¹,

Hassanpour²,

Bordbar³

2010

Journal of the Korean Chemical Society

View full text Add to dashboard Cite

ABSTRACT. In this study, iron(III)-2,4-dihydroxysalophen chloride (Fe(2,4-DHSalophen)Cl), has been synthesized by combination of 2,4-dihydroxysalophen (2,4-DHSalophen) with FeCl2 in a solvent system. This complex combination was characterized using UV-vis and IR spectroscopies. Subsequently, the interaction between native calf thymus deoxyribonucleic acid (ct-DNA) and Fe(2,4-DHSalophen)Cl, was investigated in 10 mM Tris/HCl buffer solution, pH 7.2, using UV-visible absorption and fluorescence spectroscopies, thermal denaturation technique and viscosity measurements. From spectrophotometric titration experiments, the binding constant of Fe(2,4-DHSalophen)Cl with ct-DNA was found to be (1.6 ± 0.

show abstract

Section: Viscosity Measurementssupporting

confidence: 82%

Study of Interaction of Native DNA with Iron(III)-(2,4-Dihydroxysalophen)chloride

Azani¹,

Hassanpour²,

Bordbar³

2010

Journal of the Korean Chemical Society

View full text Add to dashboard Cite

show abstract

“…The ability of a compound to alter the thermal denaturation profile of DNA is used as an indication of the binding of the compound to DNA (24). The average value of the midpoint thermal denaturation temperature for calf thymus DNA was 61.2°C.…”

mentioning

confidence: 99%

Suramin is an inhibitor of DNA topoisomerase II in vitro and in Chinese hamster fibrosarcoma cells.

Bojanowski

Lelièvre

Markovits

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

107

View full text Add to dashboard Cite

The antitrypanosomal and antifiliarial drug suramin is currently under investigation for treatment of advanced malignancies including prostatic cancer, adrenocortical cancer, and some lymphomas and sarcomas. Here we show that suramin is a potent inhibitor of the nuclear enzyme DNA topoisomerase II. Suramin inhibited purified yeast topoisomerase II with an IC5s of about 5 FM, as measured by decatenation or relaxation assays. Suramin did not stabilize the covalent DNA-topoisomerase II reaction intermediate ("cleavable complex"), whereas other inhibitors of this enzyme, such as amsacrine, etoposide, and the ellipticines, are known to stabilize the intermediate. In contrast, the presence of suramin strongly inhibited the cleavable-complex formation induced by amsacrine or etoposide. Accumulation of the endogenous cleavable complex was also inhibited. Suramin entered the nucleus of DC-3F Chinese hamster fibrosarcoma cells exposed to radiolabeled suramin for 24 hr as shown by both optic and electron microscopy. The suramin present in the nucleus seemed to interact with topoisomerase II, since suramin reduced the number of amsacrine-induced protein-associated DNA strand breaks in DC-3F cells and protected these cells from the cytotoxic action of amsacrine. Cells resistant to 9-hydroxyellipticine, which have been shown to have an altered topoisomerase II activity, are about 7-fold more resistant to suramin than the sensitive parental cells as shown by 72-hr growth inhibition assay. Our results suggest that DNA topoisomerase II is a target of suramin action and that this action may play a role in the cytotoxic activity of suramin.Suramin is a hexasulfated naphthylurea that has been used in the treatment of trypanosomiasis (sleeping sickness) and onchocerciasis for more than half a century (1). Mor recently, suramin was shown to prevent infection of T lymphocytes by human immunodeficiency virus in vitro (2). This led to clinical trials of the compound in AIDS patients, where it showed little therapeutic activity (3, 4). However, during these trials a complete clinical response was noted in a patient with Kaposi sarcoma and non-Hodgkin lymphoma (4), and subsequent studies showed that suramin was active in the treatment of several metastatic cancers such as renal cancer, adrenocarcinoma, lymphoma, and prostate cancer (5, 6).Suramin inhibits the binding of platelet-derived growth factor, epidermal growth factor, basic fibroblast growth factor, transforming growth factor /3, and insulin-like growth factor to their specific cell surface receptors (7-11). The drug also affects the activity of protein kinase C and inhibits phosphatidylinositol kinase and diacylglycerol kinase (12, 13). Several nuclear enzymes are also inhibited by suramin. These include DNA and RNA polymerases, terminal deoxynucleotidyltransferase, and reverse transcriptase (14-17).Suramin can induce cell differentiation in several different systems (18,19) and can inhibit tumor cell invasion (20).Here we demonstrate that suramin is a potent inhibitor of...

show abstract

“…It is perhaps significant that the extent of stabilisation is smaller than the effect observed for well-established intercalators such as ethidium bromide (ΔT m > 10°). 27 However, such a moderate stabilisation has been observed previously for other mononaphthalimide based DNA intercalators and perhaps suggests a weaker intercalation efficiency of 2 and 3.…”

Section: Thermal Melting Assaymentioning

confidence: 67%

The effect of the 4-amino functionality on the photophysical and DNA binding properties of alkyl-pyridinium derived 1,8-naphthalimides

et al. 2013

View full text Add to dashboard Cite

The synthesis and characterisation of two cationic pyridinium based 4-amino-1,8-naphthalimide derivatives (2 and 3) are described and compared to those of compound 1. The photophysical properties of 2 and 3 are shown to vary greatly with the solvent polarity and H-bonding ability. The dimethylamino substitution in 3 results in a weak quantum yield of fluorescence emission due to faster non-radiative deactivation of the excited singlet state than that seen for 2. As with 1, the fluorescence of 2 was found to be enhanced in its 1 : 1 complex with 5'-adenosine-monophosphate (5'-AMP) while it was partially quenched in its complex with 5'-guanosine-monophosphate (5'-GMP). In contrast, the fluorescence of 3 was enhanced ('switched on') in the presence of both adenine and guanine rich sequences. Linear and circular dichroism studies showed that each of 1, 2 and 3 binds to double-stranded DNA by intercalation. However, 2 and 3 do not show the preference for AT-rich DNA observed for 1. Comparative fluorescence studies with double stranded DNA show that the emission of 3 was 16 times enhanced in its DNA bound form, suggesting potential use of this structure as a spectroscopic probe for studying nucleic acid structure.

show abstract

Design, synthesis, and DNA binding properties of bifunctional intercalators. Comparison of polymethylene and diphenyl ether chains connecting phenanthridine

Cited by 420 publications

References 0 publications

Study of Interaction of Native DNA with Iron(III)-(2,4-Dihydroxysalophen)chloride

Study of Interaction of Native DNA with Iron(III)-(2,4-Dihydroxysalophen)chloride

Suramin is an inhibitor of DNA topoisomerase II in vitro and in Chinese hamster fibrosarcoma cells.

The effect of the 4-amino functionality on the photophysical and DNA binding properties of alkyl-pyridinium derived 1,8-naphthalimides

Contact Info

Product

Resources

About