Streptonigrin and lavendamycin partial structures. Preparation of 7‐amino‐2‐(2′‐pyridyl)quinoline‐5,8‐quinone‐6′‐carboxylic acid: A probe for the minimum, potent pharmacophore of the naturally occurring antitumor‐antibiotics

Yasuda, Masami; Boger, Dale L.

doi:10.1002/jhet.5570240504

Cited by 13 publications

(3 citation statements)

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“…In these studies, we prepared and examined a series of key partial structures and analogues of streptonigrin . These and studies of others have provided insights into the structural features of streptonigrin required for expression of its biological activity.…”

Section: Heterocyclic Azadienesmentioning

confidence: 99%

Inverse Electron Demand Diels–Alder Reactions of Heterocyclic Azadienes, 1-Aza-1,3-Butadienes, Cyclopropenone Ketals, and Related Systems. A Retrospective

2019

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A summary of the investigation and applications of the inverse electron demand Diels–Alder reaction is provided that have been conducted in our laboratory over a period that now spans more than 35 years. The work, which continues to provide solutions to complex synthetic challenges, is presented in the context of more than 70 natural product total syntheses in which the reactions served as a key strategic step in the approach. The studies include the development and use of the cycloaddition reactions of heterocyclic azadienes (1,2,4,5-tetrazines; 1,2,4-, 1,3,5-, and 1,2,3-triazines; 1,2-diazines; and 1,3,4-oxadiazoles), 1-aza-1,3-butadienes, α-pyrones, and cyclopropenone ketals. Their applications illustrate the power of the methodology, often provided concise and nonobvious total syntheses of the targeted natural products, typically were extended to the synthesis of analogues that contain deep-seated structural changes in more comprehensive studies to explore or optimize their biological properties, and highlight a wealth of opportunities not yet tapped.

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Section: Heterocyclic Azadienesmentioning

confidence: 99%

Inverse Electron Demand Diels–Alder Reactions of Heterocyclic Azadienes, 1-Aza-1,3-Butadienes, Cyclopropenone Ketals, and Related Systems. A Retrospective

2019

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“…T compounds were prepared according to the reported procedure from the l -cysteine ethyl ester and the corresponding benzaldehydes. QD was prepared by hydroxylation followed by oxidation of 5-hydroxyquinoline .…”

Section: Resultsmentioning

confidence: 99%

Antitumor Agents. 3. Design, Synthesis, and Biological Evaluation of New Pyridoisoquinolindione and Dihydrothienoquinolindione Derivatives with Potent Cytotoxic Activity

Bolognese¹,

Correale²,

Manfra³

et al. 2004

J. Med. Chem.

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New antiproliferative compounds, the 1-aryl-3-ethoxycarbonyl-pyrido[2,3-g]isoquinolin-5,10-diones (PIQDs, 1-7), were designed on the basis of a molecular model obtained by aligning the common quinolinquinone substructure of 5H-pyrido[3,2-a]phenoxazin-5-one (PPH) and some known anticancer agents. A Diels-Alder reaction between quinolin-5,8-dione (QD) and a 2-azadiene, formed by demolition of 2-aryl-1,3-thiazolidine ethyl esters (T compounds), was used to produce 1-7 and the isomeric 1-aryl-3-ethoxycarbonylpyrido[3,2-g]isoquinolin-5,10-diones (8-14). Two other compounds, the 3-amino-3-ethoxycarbonyldihydrothieno[2,3-g]quinolin-4,9-dione (15) and the 3-amino-3-ethoxycarbonyldihydrothieno[3,2-g]quinolin-4,9-dione (16), arising from a 1,4 Michael reaction of QD with a thiolate species formed by opening of T compounds, were recovered from the reaction mixture. The antiproliferative activity of 1-16 was evaluated against representative human liquid and solid neoplastic cell lines. The IC(50) of these compounds had median values in the range 2.00-0.01 microM, with 2-4 and 15 exhibiting significantly higher in vitro cytotoxic activity. Compound 2, also evaluated against KB subclones (KB(MDR), KB(7D), and KB(V20C)), was shown to be scarcely subject to the MDR1/P-glycoprotein drug efflux pump responsible for drug resistance. The noncovalent DNA-binding properties of PIQDs were examined using UV-vis and (1)H NMR spectroscopy experiments. Accordingly, these compounds were confirmed to have an ability to intercalate into double-stranded DNA by topoisomerase I superhelix unwinding assay. Interesting structure-activity relationships were found. Three important features seem to contribute to the cytotoxic activity of these anticancer ligands: (i) the DNA intercalating capability of the three-cyclic quinonic system, typical of this class of compounds, (ii) the position of the pendant phenyl ring that, according to the superimposition model, must occupy the same area of the corresponding benzo-fused ring A of PPH, and (iii) the effect of electron-withdrawing substituents on the phenyl ring, which can contribute improving the pi-pi stacking interactions between ligand and DNA base pairs. Besides, a mechanism of action suspected to involve topoisomerases could be hypothesized to interpret the antiproliferative activity of the thienoquinolindione 15, which can be regarded as a cyclic cysteine derivative.

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“…Pratt and co-workres described remarkable amoebicidal activity of 7-undecyl-6-hydroxy-5,8quinolinequinone (Pratt and Drake, 1960). Moreover, naturally occurring lavendamycin and streptonigrin containing quinoline-5,8-dione group were reported to exhibit antibiotic and antitumor activities (Yasuda and Boger, 1987). Quinoline-5,8-dione anti-cancer drugs have been known to interact with DNA , and through alkylation and chain-cutting of DNA they perform double action (Chinigos et al, 1987).…”

mentioning

confidence: 99%

Double Alkynylation of Quinoline-5,8-diones and their <i>In-silico</i> and Antimicrobial Studies

Ezeokonkwo¹,

Ja²,

Okafor³

et al. 2018

Journal of Applied Sciences and Environmental Management

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A double alkynylation of quinoline-5,8-dione to furnished bis-alkynylquinoline-5,8-dione in good yields and their in silico and antimicrobial studies is described. This was achieved by cross-coupling of 6,7dibromoquinoline-5,8-dione with various terminal alkynes in the presence of bis(triphenylphosphine) palladium(II) chloride as a pre-catalyst and tetrabutyl ammonium fluoride trihydrate. The structures of the synthesised compounds were confirmed by UV/Visible, Fourier Transform-Infrared and 1 H and 13 C-NMR spectral data. The synthesised compounds exhibited good activity against Escherichia Coli 1, Escherichia Coli 12, Klebsiella Pneumonia, Pseudomonas aeroginosa and Staphylococcus aureus compare to the gentamycin and ampicillin. Molecular docking simulation study of the binding interactions of compounds with receptors disclosed significant binding affinity for P. aeruginosa LpxC than the E. coli glutaredoxin.

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Streptonigrin and lavendamycin partial structures. Preparation of 7‐amino‐2‐(2′‐pyridyl)quinoline‐5,8‐quinone‐6′‐carboxylic acid: A probe for the minimum, potent pharmacophore of the naturally occurring antitumor‐antibiotics

Cited by 13 publications

References 64 publications

Inverse Electron Demand Diels–Alder Reactions of Heterocyclic Azadienes, 1-Aza-1,3-Butadienes, Cyclopropenone Ketals, and Related Systems. A Retrospective

Inverse Electron Demand Diels–Alder Reactions of Heterocyclic Azadienes, 1-Aza-1,3-Butadienes, Cyclopropenone Ketals, and Related Systems. A Retrospective

Antitumor Agents. 3. Design, Synthesis, and Biological Evaluation of New Pyridoisoquinolindione and Dihydrothienoquinolindione Derivatives with Potent Cytotoxic Activity

Double Alkynylation of Quinoline-5,8-diones and their <i>In-silico</i> and Antimicrobial Studies

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