Regioselective arylation of ribose in adenosine and guanosine with the antitumor drug N2-methyl-9-hydroxyellipticinium acetate.

Bernadou, Jean; Meunier, Bernard; Meunier, Gérard; Auclair, Christian; Paoletti, Claude

doi:10.1073/pnas.81.5.1297

Cited by 18 publications

(2 citation statements)

References 25 publications

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“…e oxidative bioactivation of the antitumor drug 7V2methyl-9-hydroxyellipticinium (NMHE)1 has been found to occur through peroxidase and oxidase reactions leading to the generation of the reactive quinone imine 7V2-methyl-9-oxoellipticinium (NMOE) (Scheme I) (Auclair & Paoletti, 1981;Auclair et al, 1983a;Bernadou et al, 1983). In the presence of suitable nucleophiles such as O, N, or S donor containing compounds, including amino acids, proteins, glutathione, and ribonucleosides, the oxidation of NMHE to NMOE results in the formation of covalent adducts in vitro (Auclair et al, 1983b(Auclair et al, ,c, 1984Meunier et al, 1983;Bernadou et al, 1984).…”

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confidence: 99%

Peroxidase-catalyzed covalent binding of the antitumor drug N2-methyl-9-hydroxyellipticinium to DNA in vitro

Auclair¹,

Dugue²,

Meunier³

et al. 1986

Biochemistry

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In the presence of DNA, the antitumor drug N2-methyl-9-hydroxyellipticinium (elliptinium; NMHE) [Le Pecq, J. B., Gosse, C., Dat-Xuong, N., & Paoletti, C. (1975) C. R. Seances Acad. Sci., Ser. D 281, 1365-1367] is oxidized by the horseradish peroxidase-hydrogen peroxide (HRP-H2O2) system to the quinone imine derivative N2-methyl-9-oxoellipticinium (NMOE) [Auclair, C., & Paoletti, C. (1981) J. Med. Chem. 24, 289-295], which interacts with DNA according to the intercalation mode. When excess H2O2 was used, the major part of the quinone imine was further oxidized to the o-quinone N2-methyl-9,10-dioxoellipticinium [Bernadou, J., Meunier, G., Paoletti, C., & Meunier, B. (1983) J. Med. Chem. 26, 574-579]. In the presence of stoichiometric amounts of H2O2 (H2O2/NMHE = 1), NMOE reacts with DNA, yielding a fluorescent compound irreversibly linked to the nucleic acid, which is related to the covalent binding of the ellipticinium chromophore. Under optimal reaction conditions, NMHE binding occurs according to a first-order process (k = 4.3 X 10(-3) min-1) with a linear increase with respect to drug to nucleotide ratio up to a maximum binding of 1 NMHE per 20 base pairs (r = 0.05). The fluorescence spectra (ex, 330 nm; em, 548 nm) of NMHE bound to DNA, the occurrence of energy transfer from the DNA to the drug, and the DNA length increase of the DNA-NMHE adduct suggest that the binding occurs at the intercalating site with limited denaturation of the DNA helix.(ABSTRACT TRUNCATED AT 250 WORDS)

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confidence: 99%

Peroxidase-catalyzed covalent binding of the antitumor drug N2-methyl-9-hydroxyellipticinium to DNA in vitro

Auclair¹,

Dugue²,

Meunier³

et al. 1986

Biochemistry

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“…Recent studies indicate that m-AMSA inhibits the topoisomerization and catenation reactions of DNA topoisomerase II,10 probably by trapping the enzyme-DNA complexes.11, 12 Other substances, such as etoposide (VP- 16, Figure 1), adriamycin, and ellipticine13 also stabilize the cleavable complex between DNA topoisomerase II and DNA. In the present study, we show that the incorporation of an alkylating group into some DNA intercalating agents greatly enhances their antileukemic properties.…”

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Intercalating agents with covalent bond forming capability. A novel type of potential anticancer agents. 2. Derivatives of chrysophanol and emodin

Koyama¹,

Takahashi²,

Chou³

et al. 1989

J. Med. Chem.

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Fifty-one new C-methyl-modified derivatives of the anthraquinones chrysophanol and emodin or their various methyl ethers were prepared for structure-activity relationship studies of anticancer activity against mouse leukemia L1210 and human leukemia HL-60 cells. Representative compounds were spectrophotometrically studied for their capacity to interact with natural and denatured DNA. In general, those anthraquinones bearing an amino function interact with DNA. 1,8-Dimethoxyanthraquinones are incapable of intercalating into DNA. 1- or 8-Monohydroxymono-methoxyanthraquinones, however, interact with DNA to some extent. No straightforward correlation is apparent between the DNA-affinity data of the compounds studied spectrophotometrically and their cytotoxic effects. Cytotoxic potencies of these compounds on cell growth inhibition during a 72-h period are inversely correlated to their potencies when inhibiting [3H]TdR incorporation into DNA during the initial 30 min of exposure. Surprisingly, some compounds that showed more cytotoxicity did not inhibit initial TdR incorporation (0-30 min), while some others that strongly inhibited TdR incorporation initially did not exhibit cytotoxicity in 72 h. The results suggest that the cytotoxicity produced by these compounds is time dependent and is not a direct result of initial inhibition of DNA replication.

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Design, Synthesis and Molecular Docking Studies of New Indole Scaffolds

Kotha,

Meher,

Das

et al. 2024

Asian J Org Chem

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A convenient and straightforward approach for the construction of angular and linear indole scaffolds from commercially available β‐tetralones through a sequential methylation/ allylation/ propargylation followed by ring closing metathesis (RCM)/ [2+2+2] cyclotrimerization and Fischer indolization (FI) sequence has been described. The dipropargyl derivatives were further investigated for Sonogashira cross‐coupling with iodo‐benzene and click chemistry with benzyle azide to synthesize diverse indole motifs. The [2+2+2] cyclotrimerized products were treated with 3,5‐dimethyl aniline to obtain the product that resembles the structure of Alectinib, an FDA approved drug for the treatment of cancer. The approach provides a series of indole derivatives in moderate to good yields with excellent functional group tolerance and hence these compounds are utilized for molecular docking studies which shows good results. All the compounds synthesized here are well characterized by NMR and HRMS data.

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Regioselective arylation of ribose in adenosine and guanosine with the antitumor drug N2-methyl-9-hydroxyellipticinium acetate.

Cited by 18 publications

References 25 publications

Peroxidase-catalyzed covalent binding of the antitumor drug N2-methyl-9-hydroxyellipticinium to DNA in vitro

Peroxidase-catalyzed covalent binding of the antitumor drug N2-methyl-9-hydroxyellipticinium to DNA in vitro

Intercalating agents with covalent bond forming capability. A novel type of potential anticancer agents. 2. Derivatives of chrysophanol and emodin

Design, Synthesis and Molecular Docking Studies of New Indole Scaffolds

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