Photochemical electrocyclisation of 3-vinylindoles to pyrido[2,3-a]-, pyrido[4,3-a]- and thieno[2,3-a]-carbazoles: Design, synthesis, DNA binding and antitumor cell cytotoxicity

Lemster, T.; Pindur, U.; Lenglet, Gaëlle; Depauw, Sabine; Dassi, Christelle; David-Cordonnier, Marie-Hélène

doi:10.1016/j.ejmech.2009.03.026

Cited by 59 publications

(22 citation statements)

References 20 publications

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“…11,32) Figure 1 illustrates the absorption spectra of compounds 1a, 2b, 3b, 4b and 6b in the phosphate ethylenediaminetetraacetic acid (PE) buffer (1 mM Na 2 HPO 4 , 0.1 mM ethylenediaminetetraacetic acid (EDTA), pH 7.4) in the presence of increasing amounts of CT-DNA. In all cases, the binding of the drugs to CT-DNA results in considerable spectral changes, characterized by a slight bathochromic shift and a marked hypochromic effect.…”

Section: Resultsmentioning

confidence: 99%

“…16,32) Compounds 1a, 2b, 3b, 4b and 6b present intrinsic fluorescence properties which could be used to evaluate their respective DNAbinding potency. The effect of CT-DNA on the fluorescence intensity of the selected b-carbolines 1a, 2b, 3b, 4b and 6b was determined by the use of fluorescence spectroscopy.…”

Section: Resultsmentioning

confidence: 99%

“…11,32,33) In order to confirm the DNA intercalating ability of those compounds, we investigated the stabilization of the DNA helix by the selected b-carbolines 1a, 2b, 3b, 4b and 6b using melting temperature (T m ) studies to evaluate relative affinity for DNA of the selected compounds. The T m of CT-DNA in the presence and absence of compounds 1a, 2b, 3b, 4b and 6b were obtained from melting curves (not shown) and the results of T m analysis performed with CT-DNA are shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Fluorescence Spectroscopy Fluorescence spectral measurement 16,32) was recorded using 10 mM of the fluorescent drugs incubated in 1 ml of PE buffer in the presence or absence of increasing concentrations of CT-DNA (0, 10, 20, 30, 40, 50, 60, 70, 80, 90 mM) in a quartz cuvette of 10 mm path length. The corresponding changes in the fluorescence intensity of the selected compounds were observed on a Shimadzu RF-5310PC spectrofluorometer at a fluorescence excitation wavelength of 372 nm.…”

Section: Cytotoxicity Assays In Vitromentioning

confidence: 99%

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Synthesis and Biological Evaluation of Novel .BETA.-Carbolines as Potent Cytotoxic and DNA Intercalating Agents

Chen

Cao

Shi

et al. 2010

CHEMICAL & PHARMACEUTICAL BULLETIN

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901Regular Article b-Carboline alkaloids represent a large number of naturally and synthetic indole alkaloids associated with a broad spectrum of biochemical effects and pharmaceutical properties.1) Previous investigations focused on the effects of b-carboline alkoloids on the central nervous system (CNS). 2-9)Recent reports [10][11][12][13][14][15][16][17] have pointed out b-carbolines as a class of potential antitumor agents, which was discovered to function their antitumor activity through multiple mechanisms, such as intercalating into DNA, 11,18) and kinesin Eg5. 25)Recently, our group investigations 26-31) on the synthesis of a variety of b-carboline derivatives and the evaluation of their antitumor activities unraveled that b-carbolines had potent antitumor activities and the activities were correlated to both the planarity of the molecule and the presence of the ring substituents. Structure-activity relationships (SARs) analysis suggested that the introduction of appropriate substituents into position-2, 3 and 9 played a vital role in determining their antitumor effects, and the n-butyl, benzyl or phenylpropyl substituents at position-9 was suitable pharmacophoric group giving rise to some potent antitumor agents.In continuing search for novel and effective antitumor agents, we designed and synthesized a series of water-soluble b-carbolines bearing a flexible alkylamino side chain at position-3 and a alkyl or arylated alkyl substituent at position-9, respectively. The selective introduction of a methyl, n-butyl, benzyl, 4-fluorobenzyl and phenylpropyl substituents into position-9 of b-carboline nucleus was based on the previous SARs analysis results, and the design of the amino substituents was limited to diethylaminoethylamino, dimethylaminopropylamino diethylaminopropylamino and diethylaminobutylamino group. The purpose of this study was to investigate effect of the flexible amino side chain moiety on the antitumor activity, with the ultimate aim of developing novel antitumor b-carbolines with improved water solubility and bioavailability. ChemistryThe synthetic routes of novel b-carbolines 1a, 2a-d, 3a-d, 4a-d, 5a-d and 6a-d are outlined in Chart 1. 1-Methyl-b-carboline-3-carboxaldehydes 1-6 were prepared from the L-tryptophan via six steps including the Pictet-Spengler condensation, esterification, aromatization, N-alkylation or N-arylation, reduction and oxidation as previously described. [26][27][28] The reaction of compounds 1-6 with the corresponding diamines to form schiff bases took place readily at room temperature in good yield. The crude schiff bases without further purification were directly reduced with NaBH 3 CN in anhydrous methanol to give the target b-carbolines 1a, 2a-d, 3a-d, 4a-d, 5a-d and 6a-d (Table 1) in 40-78% yield. The chemical structures of all the synthesized compounds were characterized by MS, IR, 1 H-NMR, and 13 C-NMR spectra. Results and DiscussionCytotoxic Activity in Vitro The cytotoxic potential of all newly synthesized b-carbolines was evaluated in vitro against a pa...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Cytotoxicity Assays In Vitromentioning

confidence: 99%

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Synthesis and Biological Evaluation of Novel .BETA.-Carbolines as Potent Cytotoxic and DNA Intercalating Agents

Chen

Cao

Shi

et al. 2010

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…DNase I footprinting experiments were performed essentially as described in Lemster et al (19) and Racané et al (20). Briefly, the 117- and 265-bp DNA fragments were obtained from EcoRI and PvuII double digestion of the pBS plasmid (Stratagene, La Jolla, CA).…”

Section: Methodsmentioning

confidence: 99%

New Insights on the Mechanism of Quinoline-based DNA Methyltransferase Inhibitors

Gros

Fleury

Nahoum

et al. 2015

Journal of Biological Chemistry

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Background: 4-Aminoquinoline SGI-1027 and analogs inhibit DNA methylation, which is deregulated in cancers.Results: These compounds induce deviations from Michaelis-Menten equations in DNA competition experiments and interact with DNA.Conclusion: They are competitive inhibitors for the DNA substrate of the DNA methyltransferase and non-competitive for the methyl group donor, S-adenosyl-l-methionine.Significance: These findings suggest a mechanism of inhibition for these 4-aminoquinoline-based DNMT inhibitors.

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An Efficient Rhodium/Oxygen Catalytic System for Oxidative Heck Reaction of Indoles and Alkenes via CH Functionalization

2014

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Photochemical electrocyclisation of 3-vinylindoles to pyrido[2,3-a]-, pyrido[4,3-a]- and thieno[2,3-a]-carbazoles: Design, synthesis, DNA binding and antitumor cell cytotoxicity

Cited by 59 publications

References 20 publications

Synthesis and Biological Evaluation of Novel .BETA.-Carbolines as Potent Cytotoxic and DNA Intercalating Agents

Synthesis and Biological Evaluation of Novel .BETA.-Carbolines as Potent Cytotoxic and DNA Intercalating Agents

New Insights on the Mechanism of Quinoline-based DNA Methyltransferase Inhibitors

An Efficient Rhodium/Oxygen Catalytic System for Oxidative Heck Reaction of Indoles and Alkenes via CH Functionalization

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