The ‘Other’ Telomerase Inhibitors: Non-G-Quadruplex Interactive Agent, Non-Antisense, Non-Reverse Transcriptase Telomerase Inhibitors

2002 ◽  
Vol 2 (5) ◽  
pp. 589-603 ◽  
Author(s):  
L. Beltz
Keyword(s):  
Reverse Transcriptase ◽  
Telomerase Inhibitors ◽  
G Quadruplex

scholarly journals Design and study of telomerase inhibitors based on G-quadruplex ligands

2013 ◽  
Vol 29 (3) ◽  
pp. 169-176 ◽  
Author(s):  
V. V. Negrutska ◽  
L. V. Dubey ◽  
M. M. Ilchenko ◽  
I. Ya. Dubey
Keyword(s):  
Telomerase Inhibitors ◽  
G Quadruplex

Novel ruthenium(ii) polypyridyl complexes as G-quadruplex stabilisers and telomerase inhibitors

2014 ◽  
Vol 43 (21) ◽  
pp. 7811 ◽  
Author(s):  
Guoliang Liao ◽  
Xiang Chen ◽  
Jingheng Wu ◽  
Chen Qian ◽  
Hanqiang Wang ◽  
...  
Keyword(s):  
Polypyridyl Complexes ◽  
Telomerase Inhibitors ◽  
G Quadruplex

Inhibition of Protein Synthesis Through RNA-Based Tandem G-Quadruplex Formation

2021 ◽  
Author(s):  
Masaki Hagihara
Keyword(s):  
Protein Synthesis ◽  
Reverse Transcriptase ◽  
Repeat Sequences ◽  
Guanine Quadruplex ◽  
G Quadruplex ◽  
Inhibition Of Protein Synthesis ◽  
Quadruplex Formation

Tandem guanine repeat sequences can adopt guanine quadruplex (G-quadruplex) structures and consecutive guanine repeat sequences can potentially afford multiple G-quadruplex structures. By using a reverse transcriptase stop assay and biophysical...

scholarly journals Selective Binding of Distamycin A Derivative to G-Quadruplex Structure [d(TGGGGT)]4

2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
Bruno Pagano ◽  
Iolanda Fotticchia ◽  
Stefano De Tito ◽  
Carlo A. Mattia ◽  
Luciano Mayol ◽  
...  
Keyword(s):  
Small Molecules ◽  
Titration Calorimetry ◽  
Distamycin A ◽  
Structural Modifications ◽  
Telomerase Inhibitors ◽  
G Quadruplex ◽  
Nmr Techniques ◽  
Eukaryotic Organisms ◽  
New Anticancer Drugs ◽  
Binding Behaviour

Guanine-rich nucleic acid sequences can adopt G-quadruplex structures stabilized by layers of four Hoogsteen-paired guanine residues. Quadruplex-prone sequences are found in many regions of human genome and in the telomeres of all eukaryotic organisms. Since small molecules that target G-quadruplexes have been found to be effective telomerase inhibitors, the identification of new specific ligands for G-quadruplexes is emerging as a promising approach to develop new anticancer drugs. Distamycin A is known to bind to AT-rich sequences of duplex DNA, but it has recently been shown to interact also with G-quadruplexes. Here, isothermal titration calorimetry (ITC) and NMR techniques have been employed to characterize the interaction between a dicationic derivative of distamycin A (compound1) and the [d(TGGGGT)]4quadruplex. Additionally, to compare the binding behaviour of netropsin and compound1to the same target, a calometric study of the interaction between netropsin and [d(TGGGGT)]4has been performed. Experiments show that netropsin and compound1are able to bind to [d(TGGGGT)]4with good affinity and comparable thermodynamic profiles. In both cases the interactions are entropically driven processes with a small favourable enthalpic contribution. Interestingly, the structural modifications of compound1decrease the affinity of the ligand toward the duplex, enhancing the selectivity.

New dimeric carbazole–benzimidazole mixed ligands for the stabilization of human telomeric G-quadruplex DNA and as telomerase inhibitors. A remarkable influence of the spacer

2015 ◽  
Vol 13 (30) ◽  
pp. 8335-8348 ◽  
Author(s):  
Basudeb Maji ◽  
Krishan Kumar ◽  
K. Muniyappa ◽  
Santanu Bhattacharya
Keyword(s):  
Dna Binding ◽  
Inhibition Activity ◽  
Telomerase Inhibition ◽  
Quadruplex Dna ◽  
Telomerase Inhibitors ◽  
Mixed Ligands ◽  
G Quadruplex

G-quadruplex DNA binding dimeric ligands and their telomerase inhibition activity are reported.

scholarly journals QSAR, pharmacophore modeling and molecular docking studies to identify structural alerts for some nitrogen heterocycles as dual inhibitor of telomerase reverse transcriptase and human telomeric G-quadruplex DNA

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
R. D. Jawarkar ◽  
R. L. Bakal ◽  
P. N. Khatale ◽  
Israa Lewaa ◽  
Chetan M. Jain ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Carbon Atom ◽  
Reverse Transcriptase ◽  
Qsar Model ◽  
Pharmacophore Modeling ◽  
Telomerase Reverse Transcriptase ◽  
Quadruplex Dna ◽  
Pharmacophore Modelling ◽  
G Quadruplex ◽  
Dual Inhibition

Abstract Background Telomerase reverse transcriptase (TERT) and human telomeric G-quadruplex DNA are amongst the favorable target for researchers to discover novel and more effective anticancer agents. To understand and elucidate structure activity relationship and mechanism of inhibition of telomerase reverse transcriptase (TERT) and human telomeric G-quadruplex DNA, a QSAR modeling and molecular docking were conducted. Results Two robust QSAR model were obtained which consist of full set QSAR model (R2: 0.8174, CCCtr: 0.8995, Q2loo: 0.7881, Q2LMO: 0.7814) and divided set QSAR model (R2: 0.8217, CCCtr: 0.9021, Q2loo: 0.7886, Q2LMO: 0.7783, Q2-F1: 0.7078, Q2-F2: 0.6865, Q2-F3: 0.7346) for envisaging the inhibitory activity of telomerase reverse transcriptase (TERT) and human telomeric G-quadruplex DNA. The analysis reveals that carbon atom exactly at 3 bonds from aromatic carbon atom, nitrogen atom exactly at six bonds from planer nitrogen atom, aromatic carbon atom within 2 A0 from the center of mass of molecule and occurrence of element hydrogen within 2 A0 from donar atom are the key pharmacophoric features important for dual inhibition of TERT and human telomeric G-quadruplex DNA. To validate this analysis, pharmacophore modeling and the molecular docking is performed. Molecular docking analysis support QSAR analysis and revealed that, dual inhibition of TERT and human telomeric DNA is mainly contributed from hydrophobic and hydrogen bonding interactions. Conclusion The findings of molecular docking, pharmacophore modelling, and QSAR are all consistent and in strong agreement. The validated QSAR analyses can detect structural alerts, pharmacophore modelling can classify a molecule's consensus pharmacophore involving hydrophobic and acceptor regions, whereas docking analysis can reveal the mechanism of dual inhibition of telomerase reverse transcriptase (TERT) and human telomeric G-quadruplex DNA. The combination of QSAR, pharmacophore modeling and molecular docking may be useful for the future drug design of dual inhibitors to combat the devastating issue of resistance. Graphical abstract

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