Human telomerase inhibition by substituted acridine derivatives

Harrison, R. John; Gowan, Sharon; Kèlland, Lloyd R.; Neidle, Stephen

doi:10.1016/s0960-894x(99)00394-7

Cited by 162 publications

(114 citation statements)

References 25 publications

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“…The number of G4 ligands has grown rapidly over a few years: a range of molecules has been shown to inhibit telomerase through binding to its substrate [14,26,27,36,[44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59]. On the other hand, few natural products have been reported as G-quadruplex-mediated telomerase inhibitors, although one, telomestatin, is exceptionally potent with an IC50 of 5 nM against telomerase [25].…”

Section: Discussionmentioning

confidence: 99%

Ascididemin and meridine stabilise G-quadruplexes and inhibit telomerase in vitro

Guittat

Cian

Rosu

et al. 2005

Biochimica et Biophysica Acta (BBA) - General Subjects

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Ascididemin and Meridine are two marine compounds with pyridoacridine skeletons known to exhibit interesting antitumour activities. These molecules have been reported to behave like DNA intercalators. In this study, dialysis competition assay and mass spectrometry experiments were used to determine the affinity of ascididemin and meridine for DNA structures among duplexes, triplexes, quadruplexes and single-strands. Our data confirm that ascididemin and meridine interact with DNA but also recognize triplex and quadruplex structures. These molecules exhibit a significant preference for quadruplexes over duplexes or single-strands. Meridine is a stronger quadruplex ligand and therefore a stronger telomerase inhibitor than ascididemin (IC 50 =ll and >80 µM, respectively in a standard TRAP assay).

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Section: Discussionmentioning

confidence: 99%

Ascididemin and meridine stabilise G-quadruplexes and inhibit telomerase in vitro

Guittat

Cian

Rosu

et al. 2005

Biochimica et Biophysica Acta (BBA) - General Subjects

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“…3,6 disubstituted acridine derivatives have been proposed by Harrison et al [12] and this study states as the planar aromatic chromophore ring which stabilize, binds to G-Quadruplex and inhibits telomerase. The protonated heterocyclic nitrogen atom (Compound 5) at physiological pH interacts G-quadruplex by increasing electron deficiency (IC 50 1.35 µM) [13].…”

Section: Acridine Derivativesmentioning

confidence: 86%

“…Wheelhouse et al [24] reported cationic porphyrins, and among them, they found one of the Compound 23 (TMPyP4- [5,[10][11][12][13][14][15]20-tetra-(-N-Methyl-4-pyridyl)] porphine) as it stabilizes and stacked with G-Quadruplex DNA and inhibits telomerase enzyme with an IC 50 value of 6.5±1.4 µM. Analogs of TMPyP4 (e.g., Compound 24 -IC 50 5 µM) have been reported and found as the positively charged substituent's on meso positions, and the size of substitution are important, and the face of porphyrins should be available for stacking [25].…”

Section: Porphyrine Derivativesmentioning

confidence: 99%

G-Quadruplex Ligands as Stabilizer Targeting Telomerase Enzyme as Anti Cancer Agents

2017

Asian J Pharm Clin Res

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The human telomere stabilization with G-Quadruplex DNA tends to induce apoptosis. The molecular target of telomere cascade with a rigid molecular may show efficacious to treat cancer. The study of intercalation to human telomeric DNA with proposed ligand can be evaluated by the help of biophysical studies and biological studies. G-Quadruplex is one of the key epigenetic episodes of eukaryotes and prokaryotes, generally found in the telomeric end region, immunoglobulin switch recombination and the lagging strand of the DNA. These chemotherapeutic advances are not enough to maintain a life expectancy of cancer affected patients. A number of G-Quadruplex ligands such as acridine, perylene, and anthraquinones have been synthesized reported and evaluated them for the inhibitor activity. Therefore, translational research can pave the novel prospect to treat cancer in a fundamental way. In that connection, basic research showed G-Quadruplex phenomenon of DNA, which is having a great impact in this chemotherapy.

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“…Lond. B (2002) diamidoanthraquinones (Perry et al 1998a,b), porphyrin derivatives (Fedoroff et al 1998), acridines (Harrison et al 1999) and uorenones . These drugs cause telomerase inhibition and growth arrest, but corresponding telomere shortening and the predicted lag phase have not been demonstrated .…”

Section: (Iv) Targeting the Telomeres G-quadruplex Interacting Agentsmentioning

confidence: 99%

Tiptoeing to chromosome tips: facts, promises and perils of today's human telomere biology

Fajkus

Šimíčková

Maláska

2002

Phil. Trans. R. Soc. Lond. B

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The past decade has witnessed an explosion of knowledge concerning the structure and function of chromosome terminal structures-telomeres. Today's telomere research has advanced from a pure descriptive approach of DNA and protein components to an elementary understanding of telomere metabolism, and now to promising applications in medicine. These applications include 'passive' ones, among which the use of analysis of telomeres and telomerase (a cellular reverse transcriptase that synthesizes telomeres) for cancer diagnostics is the best known. The 'active' applications involve targeted downregulation or upregulation of telomere synthesis, either to mortalize immortal cancer cells, or to rejuvenate mortal somatic cells and tissues for cellular transplantations, respectively. This article reviews the basic data on structure and function of human telomeres and telomerase, as well as both passive and active applications of human telomere biology.

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Human telomerase inhibition by substituted acridine derivatives

Cited by 162 publications

References 25 publications

Ascididemin and meridine stabilise G-quadruplexes and inhibit telomerase in vitro

Ascididemin and meridine stabilise G-quadruplexes and inhibit telomerase in vitro

G-Quadruplex Ligands as Stabilizer Targeting Telomerase Enzyme as Anti Cancer Agents

Tiptoeing to chromosome tips: facts, promises and perils of today's human telomere biology

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