A novel inhibitor of human telomerase derived from 10H-indolo[3,2-b]quinoline

Caprio, Vittorio; Guyen, Berengere; Opoku-Boahen, Yaw; Mann, John; Gowan, Sharon; Kelland, Lloyd; Read, Martin A.; Neidle, Stephen

doi:10.1016/s0960-894x(00)00378-4

Cited by 106 publications

(58 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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

View full text Add to dashboard Cite

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).

show abstract

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

View full text Add to dashboard Cite

show abstract

“…The non-folded, single-stranded form of the primer is required for optimal telomerase activity and qua-druplex formation has been shown to directly inhibit telomerase elongation in vitro [20]. A growing number of small molecules have been discovered to inhibit telomerase activ ity by inducing and/or stabilizing G-quartet structure [45,46], including l0H-indolo [3,2-b] quinoline derivatives [47]. Therefore, here, we performed a TRAP assay with increasing concentrations (ranging from 1 to 50 µM) of the compound.…”

Section: Telomerase Inhibitionmentioning

confidence: 99%

Interactions of cryptolepine and neocryptolepine with unusual DNA structures

et al. 2003

View full text Add to dashboard Cite

1 These authors contributed equally to this work. AbstractCryptolepine, the main alkaloid present in the roots of Cryptolepis sanguinolenta, presents a large spectrum of biological properties. It has been reported to behave like a DNA intercalator with a preference for GC-rich sequences. In this study, dialysis competition assay and mass spectrometry experiments were used to determine the affinity of cryptolepine and neocryptolepine for DNA structures among duplexes, triplexes, quadruplexes and single strands. Our data confirm that cryptolepine and neocryptolepine prefer GC over AT-rich duplex sequences, but also recognize triplex and quadruplex structures. These compounds are weak telomerase inhibitors and exhibit a significant preference for triplexes over quadruplexes or duplexes.

show abstract

“…Several classes of small molecules have been identified to interact with and stabilize G-quadruplexes, including tricyclic anthraquinones (20), fluorenones (21), substituted acridines (22,23), cationic porphyrins (24,25), telomestatin (SOT-095; ref. 26), a perylenetetracarboxylic diimide derivative (27), indoloquinolines (28), pyridinedicarboxamide derivatives (29), and a benzonaphthofurandione tetracyclic compound (30). Cryptolepine is a naturally occurring quindoline alkaloid.…”

Section: Introductionmentioning

confidence: 99%

“…Cryptolepine is also a rare example of natural product whose preparation was reported before its isolation from natural resource. Recent studies have revealed that some structural derivatives of cryptolepine were capable of interacting with G-quadruplex forms of DNA and inhibiting the activity of telomerase (28,31).…”

Section: Introductionmentioning

confidence: 99%

G-quadruplex ligand SYUIQ-5 induces autophagy by telomere damage and TRF2 delocalization in cancer cells

Zhou

Deng

Zhang

et al. 2009

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Agents stabilizing G-quadruplexes have the potential to destroy the functional structure of telomere and could therefore act as antitumor agents. We previously reported that SYUIQ-5 could stabilize G-quadruplex, induce senescence, and inhibit c-myc gene promoter activity. In this study, we showed that SYUIQ-5 inhibited proliferation of CNE2 and HeLa cancer cells, triggered a rapid and potent telomere DNA damage response characterized by the formation of telomeric foci γ-H2AX, and obviously induced autophagy with the features of increased LC3-II and a punctuated pattern of YFP-LC3 fluorescence. These phenomena may primarily depend on the delocalization of TRF2 from telomere, which was further degraded by proteasomes. Furthermore, overexpression of TRF2 inhibited SYUIQ-5-induced γ-H2AX expression. Also, ATM was activated following SYUIQ-5 treatment. The pretreatment with ATM inhibitor ku55933 and ATM siRNA effectively reduced the production of γ-H2AX and LC3-II. ATM knockdown partially antagonized the anticancer effects of SYUIQ-5. Moreover, inhibition of autophagy by short hairpin RNA against the autophagy-related gene ATG5 attenuated the cytotoxicity of SYUIQ-5. These results indicated that SYUIQ-5 triggered potent telomere damage through TRF2 delocalization from telomeres, and eventually induced autophagic cell death in cancer cells. Our findings exhibit a novel mechanism that is responsible for the antitumor effects of SYUIQ-5. [Mol Cancer Ther 2009;8 (12):3203-13]

show abstract

A novel inhibitor of human telomerase derived from 10H-indolo[3,2-b]quinoline

Cited by 106 publications

References 11 publications

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

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

Interactions of cryptolepine and neocryptolepine with unusual DNA structures

G-quadruplex ligand SYUIQ-5 induces autophagy by telomere damage and TRF2 delocalization in cancer cells

Contact Info

Product

Resources

About