Antitumour polycyclic acridines. Part 1. Synthesis of 7H-pyrido- and 8H-quino-[4,3,2-kl]acridines by Graebe–Ullmann thermolysis of 9-(1,2,3-triazol-1-yl)acridines: application of differential scanning calorimetry to predict optimum cyclisation conditions

Hagan, Damien J.; Giménez‐Arnau, Elena; Schwalbe, Carl H.; Stevens, Malcolm F. G.

doi:10.1039/a702299i

Cited by 44 publications

(62 citation statements)

References 9 publications

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“…The product was collected and washed with water to yield the quinoacridine (87%) which was identical (mp, UV, IR, 1 H and 13 C NMR) with an authentic sample. 12 Using diethylene glycol as thermolysis medium afforded the same quinoacridine (93%).…”

Section: Methodsmentioning

confidence: 99%

“…The product was identical (UV, IR, 1 H and 13 C NMR) with an authentic sample. 12 The same quinoacridine (74%) was formed when 9-(6-nitro-1,2,3-benzotriazolyl)acridine (16d) was thermolyzed in refluxing triglyme (3.5 h) and the solution diluted with water to precipitate the product.…”

Section: Methodsmentioning

confidence: 99%

“…The product was identical (UV, IR, 1 H and 13 C NMR) to an authentic sample. 12 (ii) 9-(3-Aminoanilino)acridine (18c) 34 was converted to 9-(3-azidoanilino)acridine (18d) by sequential diazotization/azidation. The azide free base (82%) was crystallized from ethyl acetate-MeOH: mp 196-200°C dec; UV 203.5, 225.9, 246.5, 410 nm; IR 3023 (NH), 2116 (N3), 1584, 1485 cm -1 ; m/z (EI) 311 (M + ).…”

Section: Methodsmentioning

confidence: 99%

“…12 In the present work reduction of 17d with Raney nickel-hydrazine hydrate in ethanol or tin(II) chloride dihydrate in refluxing ethanol was no more efficient: the optimum conditions (95% yield) were tin(II) chloride in 12 M HCl. A more elegant approach to the amine 17e was considered feasible if a nitrenium ion (19) T π-carbocation (19′) reactive species could be generated from a suitable precursor such as the azidoaniline 18d: a sequence nitroanilinoacridine 18a f hydroxylamine 18b f reactive species 19 f intermediate 20 f 17e (Scheme 4) is typical of intramolecular cyclizations developed especially by Abramovitch.…”

Section: Introductionmentioning

confidence: 92%

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Antitumor Polycyclic Acridines. 7. Synthesis and Biological Properties of DNA Affinic Tetra- and Pentacyclic Acridines

et al. 2000

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New synthetic routes to a series of tetra- and pentacyclic acridines related in structure to marine natural products are reported. The novel water-soluble agent dihydroindolizino[7,6,5-kl]acridinium chloride 14 has inhibitory activity in a panel of non-small-cell lung and breast tumor cell lines exceeding that of m-AMSA. The salt inhibited the release of minicircle products of kDNA confirming that disorganization of topoisomerase II partly underlies the activity of the compound. COMPARE analysis of the NCI mean graph profile of compound 14 at the GI(50) level corroborates this conclusion with Pearson correlation coefficients (>0.6) to clinical agents of the topoisomerase II class: however, this correlation was not seen at the LC(50) level. The inhibitory action of 14 on Saccharomyces cerevisiae transfected with human topoisomerase II isoforms showed a 3-fold selectivity against the IIalpha isoform over the IIbeta isoform. Unlike m-AMSA, 14 is not susceptible to P-glycoprotein-mediated drug efflux and retains activity in lung cells with derived resistance to the topoisomerase II inhibitor etoposide.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%

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Antitumor Polycyclic Acridines. 7. Synthesis and Biological Properties of DNA Affinic Tetra- and Pentacyclic Acridines

et al. 2000

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“…Stevens, University of Nottingham, according to methods described earlier. [8,9] The dry-state compound was stored in the dark at 4 8C. A stock solution of DH208 was prepared by dissolving the dry compound directly in water.…”

Section: Methodsmentioning

confidence: 99%

A Novel Methodological Approach for the Analysis of Host–Ligand Interactions

Strat¹,

Missailidis

Drake

2007

ChemPhysChem

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Traditional analysis of drug-binding data relies upon the Scatchard formalism. These methods rely upon the fitting of a linear equation providing intercept and gradient data that relate to physical properties, such as the binding constant, cooperativity coefficients and number of binding sites. However, the existence of different binding modes with different binding constants makes the implementation of these models difficult. This article describes a novel approach to the binding model of host-ligand interactions by using a derived analytical function describing the observed signal. The benefit of this method is that physically significant parameters, that is, binding constants and number of binding sites, are automatically derived by the use of a minimisation routine. This methodology was utilised to analyse the interactions between a novel antitumour agent and DNA. An optical spectroscopy study confirms that the pentacyclic acridine derivative (DH208) binds to nucleic acids. Two binding modes can be identified: a stronger one that involves intercalation and a weaker one that involves oriented outer-sphere binding. In both cases the plane of the bound acridine ring is parallel to the nucleic acid bases, orthogonal to the phosphate backbone. Ultraviolet (UV) and circular dichroism (CD) data were fitted using the proposed model. The binding constants and the number of binding sites derived from the model remained consistent across the different techniques used. The different wavelengths at which the measurements were made maintained the coherence of the results.

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Continuous‐Flow Synthesis of 1‐Substituted Benzotriazoles from Chloronitrobenzenes and Amines in a CN Bond Formation/Hydrogenation/Diazotization/Cyclization Sequence

Chen

Buchwald

2013

Angewandte Chemie

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Antitumour polycyclic acridines. Part 1. Synthesis of 7H-pyrido- and 8H-quino-[4,3,2-kl]acridines by Graebe–Ullmann thermolysis of 9-(1,2,3-triazol-1-yl)acridines: application of differential scanning calorimetry to predict optimum cyclisation conditions

Cited by 44 publications

References 9 publications

Antitumor Polycyclic Acridines. 7. Synthesis and Biological Properties of DNA Affinic Tetra- and Pentacyclic Acridines

Antitumor Polycyclic Acridines. 7. Synthesis and Biological Properties of DNA Affinic Tetra- and Pentacyclic Acridines

A Novel Methodological Approach for the Analysis of Host–Ligand Interactions

Continuous‐Flow Synthesis of 1‐Substituted Benzotriazoles from Chloronitrobenzenes and Amines in a CN Bond Formation/Hydrogenation/Diazotization/Cyclization Sequence

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