Binding of anticancer drug daunomycin to parallel G-quadruplex DNA [d-(TTGGGGT)]4 leads to thermal stabilization: A multispectroscopic investigation

2018 ◽  
Vol 120 ◽  
pp. 1965-1974 ◽  
Author(s):  
Zia Tariq ◽  
Ritu Barthwal
Keyword(s):  
Anticancer Drug ◽  
Thermal Stabilization ◽  
Quadruplex Dna ◽  
G Quadruplex

Controlling anticancer drug mediated G-quadruplex formation and stabilization by a molecular container

2018 ◽  
Vol 20 (11) ◽  
pp. 7808-7818 ◽  
Author(s):  
Sagar Satpathi ◽  
Reman K. Singh ◽  
Arnab Mukherjee ◽  
Partha Hazra
Keyword(s):  
Anticancer Drug ◽  
Quadruplex Dna ◽  
Emission Color ◽  
Molecular Container ◽  
G Quadruplex ◽  
Quadruplex Formation

G-quadruplex DNA (GQ-DNA) formation has been controlled using a molecular container, cucurbit[7]uril (CB7), by means of translocating a potential anticancer drug, topotecan, from GQ-DNA to the CB7 nanocavity. Interestingly, this whole cycle can be easily monitored through the change in the emission color of the stabilizing ligand, i.e., topotecan.

Molecular recognition of parallel quadruplex [d-(TTGGGGT)]4 by mitoxantrone: binding with 1 : 4 stoichiometry leads to telomerase inhibition

RSC Advances ◽  
2016 ◽  
Vol 6 (75) ◽  
pp. 71652-71661 ◽  
Author(s):  
Tarikere Palakshan Pradeep ◽  
Sweta Tripathi ◽  
Ritu Barthwal
Keyword(s):  
Molecular Recognition ◽  
Thermal Stabilization ◽  
Cancer Drug ◽  
Telomerase Inhibition ◽  
Quadruplex Dna ◽  
Anti Cancer ◽  
G Quadruplex ◽  
Cd Studies

NMR and CD studies show that anti-cancer drug mitoxantrone (MTX) binds to parallel G-quadruplex DNA [d-(TTGGGGT)4] as stacked dimer at grooves leading to increase in thermal stabilization of DNA by ~25 °C and inhibits telomerase with IC50 = 2 μM.

scholarly journals Molecular Recognition of Parallel G-quadruplex [d-(TTGGGGT)]4 Containing Tetrahymena Telomeric DNA Sequence by Anticancer Drug Daunomycin: NMR-Based Structure and Thermal Stability

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2266 ◽  
Author(s):  
Ritu Barthwal ◽  
Zia Tariq
Keyword(s):  
Anticancer Drug ◽  
Topoisomerase Ii ◽  
Specific Interaction ◽  
Thermal Stabilization ◽  
Telomere Maintenance ◽  
Telomeric Dna ◽  
Groove Binding ◽  
Telomerase Inhibitors ◽  
G Quadruplex ◽  
Dynamics Simulations

The anticancer drug daunomycin exerts its influence by multiple strategies of action to interfere with gene functioning. Besides inhibiting DNA/RNA synthesis and topoisomerase-II, it affects the functional pathway of telomere maintenance by the telomerase enzyme. We present evidence of the binding of daunomycin to parallel-stranded tetramolecular [d-(TTGGGGT)]4 guanine (G)-quadruplex DNA comprising telomeric DNA from Tetrahymena thermophilia by surface plasmon resonance and Diffusion Ordered SpectroscopY (DOSY). Circular Dichroism (CD) spectra show the disruption of daunomycin dimers, suggesting the end-stacking and groove-binding of the daunomycin monomer. Proton and phosphorus-31 Nuclear Magnetic Resonance (NMR) spectroscopy show a sequence-specific interaction and a clear proof of absence of intercalation of the daunomycin chromophore between base quartets or stacking between G-quadruplexes. Restrained molecular dynamics simulations using observed short interproton distance contacts depict interaction at the molecular level. The interactions involving ring A and daunosamine protons, the stacking of an aromatic ring of daunomycin with a terminal G6 quartet by displacing the T7 base, and external groove-binding close to the T1–T2 bases lead to the thermal stabilization of 15 °C, which is likely to inhibit the association of telomerase with telomeres. The findings have implications in the structure-based designing of anthracycline drugs as potent telomerase inhibitors.

scholarly journals A novel square-planar Pt(ii) complex as a monomeric and dimeric G-quadruplex DNA binder

RSC Advances ◽  
2018 ◽  
Vol 8 (41) ◽  
pp. 23257-23261 ◽  
Author(s):  
Chun-Qiong Zhou ◽  
Zi-Qi Li ◽  
Ting-Cong Liao ◽  
Tian-Zhu Ma ◽  
Shuo-Bin Chen ◽  
...  
Keyword(s):  
Thermal Stabilization ◽  
Coumarin Derivative ◽  
Binding Properties ◽  
Quadruplex Dna ◽  
High Binding ◽  
Square Planar ◽  
G Quadruplex

A phenanthroimidazole ethylenediamine Pt(ii) complex with coumarin derivative (1) showed high binding properties and thermal stabilization for dimeric quadruplexes G2T1.

Hybrid Imidazole-Pyridine Derivatives: An Approach to Novel Anticancer DNA Intercalators

2020 ◽  
Vol 27 (1) ◽  
pp. 154-169 ◽  
Author(s):  
Claudiu N. Lungu ◽  
Bogdan Ionel Bratanovici ◽  
Maria Mirabela Grigore ◽  
Vasilichia Antoci ◽  
Ionel I. Mangalagiu
Keyword(s):  
Experimental Data ◽  
Antimicrobial Properties ◽  
Qsar Model ◽  
Therapeutic Effectiveness ◽  
Computational Results ◽  
Pyridine Derivatives ◽  
Quadruplex Dna ◽  
Dna Intercalators ◽  
Structure Activity ◽  
G Quadruplex

Lack of specificity and subsequent therapeutic effectiveness of antimicrobial and antitumoral drugs is a common difficulty in therapy. The aim of this study is to investigate, both by experimental and computational methods, the antitumoral and antimicrobial properties of a series of synthesized imidazole-pyridine derivatives. Interaction with three targets was discussed: Dickerson-Drew dodecamer (PDB id 2ADU), G-quadruplex DNA string (PDB id 2F8U) and DNA strain in complex with dioxygenase (PDB id 3S5A). Docking energies were computed and represented graphically. On them, a QSAR model was developed in order to further investigate the structure-activity relationship. Results showed that synthesized compounds have antitumoral and antimicrobial properties. Computational results agreed with the experimental data.

Emerging Role of G-quadruplex DNA as Target in Anticancer Therapy

2017 ◽  
Vol 22 (44) ◽  
pp. 6612-6624 ◽  
Author(s):  
Graziella Cimino-Reale ◽  
Nadia Zaffaroni ◽  
Marco Folini
Keyword(s):  
Anticancer Therapy ◽  
Quadruplex Dna ◽  
G Quadruplex
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