scholarly journals Naphthalenediimide-Linked Bisbenzimidazole Derivatives as Telomeric G-Quadruplex-Stabilizing Ligands with Improved Anticancer Activity

ACS Omega ◽  
2017 ◽  
Vol 2 (3) ◽  
pp. 966-980 ◽  
Author(s):  
Souvik Sur ◽  
Vinod Tiwari ◽  
Devapriya Sinha ◽  
Mohammad Zahid Kamran ◽  
Kshatresh Dutta Dubey ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
G Quadruplex ◽  
Stabilizing Ligands

scholarly journals G4-Selective Ligand Induced Autophagy

2021 ◽  
Author(s):  
Piyali Majumder ◽  
Chinmayee Shukla ◽  
Bhaskar Datta
Keyword(s):  
Gene Regulation ◽  
Negative Regulator ◽  
Homeostatic Mechanism ◽  
Selective Ligand ◽  
Carbocyanine Dye ◽  
G Quadruplex ◽  
Selective Ligands ◽  
Functional Context ◽  
Stabilizing Ligands ◽  
Mtor Activity

G-quadruplex (G4) structures have emerged as singular therapeutic targets for cancer and neurodegeneration. Autophagy is a housekeeping cellular homeostatic mechanism and deregulation of autophagy is common in cancer and in neurodegenerative diseases. In this study, we identified the presence of 46 putative G4 sequences in the MTOR gene by use of QGRS mapper tool. We sought to connect these putative G4 sequences to a functional context by leveraging G4-targeting ligands. A G4-selective dimeric carbocyanine dye Bis-4,3 and the porphyrin TMPyP4 were used to affect the replication, transcription and translation of the MTOR gene. The ligand-induced induction of autophagic pathway via MTOR gene regulation was monitored upon treatment of HeLa and SHSY-5Y cells with G4-targeting ligands. The use of Bis-4,3 was compared with the known G4-stabilizing activity of TMPyP4. Our results show that treatment with G4-selective ligands downregulates mTOR activity and leads to the induction of excessive autophagy. This is first report on effect of G4-selective ligands on MTOR regulation and mTOR expression. mTOR being the key negative regulator of autophagy, the current work suggests potential of G4 stabilizing ligands towards induction of autophagy through the downregulation of mTOR.

scholarly journals On the interaction of an anticancer trisubstituted naphthalene diimide with G-quadruplexes of different topologies: a structural insight

2020 ◽  
Vol 48 (21) ◽  
pp. 12380-12393
Author(s):  
Chiara Platella ◽  
Marko Trajkovski ◽  
Filippo Doria ◽  
Mauro Freccero ◽  
Janez Plavec ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Dissociation Constants ◽  
Therapeutic Potential ◽  
In Vivo Studies ◽  
Binding Modes ◽  
Hybrid Topology ◽  
Naphthalene Diimide ◽  
G Quadruplex ◽  
Naphthalene Diimides

Abstract Naphthalene diimides showed significant anticancer activity in animal models, with therapeutic potential related to their ability to strongly interact with G-quadruplexes. Recently, a trifunctionalized naphthalene diimide, named NDI-5, was identified as the best analogue of a mini-library of novel naphthalene diimides for its high G-quadruplex binding affinity along with marked, selective anticancer activity, emerging as promising candidate drug for in vivo studies. Here we used NMR, dynamic light scattering, circular dichroism and fluorescence analyses to investigate the interactions of NDI-5 with G-quadruplexes featuring either parallel or hybrid topology. Interplay of different binding modes of NDI-5 to G-quadruplexes was observed for both parallel and hybrid topologies, with end-stacking always operative as the predominant binding event. While NDI-5 primarily targets the 5′-end quartet of the hybrid G-quadruplex model (m-tel24), the binding to a parallel G-quadruplex model (M2) occurs seemingly simultaneously at the 5′- and 3′-end quartets. With parallel G-quadruplex M2, NDI-5 formed stable complexes with 1:3 DNA:ligand binding stoichiometry. Conversely, when interacting with hybrid G-quadruplex m-tel24, NDI-5 showed multiple binding poses on a single G-quadruplex unit and/or formed different complexes comprising two or more G-quadruplex units. NDI-5 produced stabilizing effects on both G-quadruplexes, forming complexes with dissociation constants in the nM range.

scholarly journals Discovery of G-quadruplex stabilizing ligands through direct ELISA of a one-bead-one-compound library

2006 ◽  
Vol 4 (23) ◽  
pp. 4364 ◽  
Author(s):  
James E. Redman ◽  
Sylvain Ladame ◽  
Anthony P. Reszka ◽  
Stephen Neidle ◽  
Shankar Balasubramanian
Keyword(s):  
Compound Library ◽  
G Quadruplex ◽  
Direct Elisa ◽  
Stabilizing Ligands

Anticancer Activity for Targeting Telomeric G-Quadruplex and Antiangiogenesis of a Novel Ru(II)–Se Complex

2014 ◽  
Vol 157 (2) ◽  
pp. 175-182 ◽  
Author(s):  
Lijun Wang ◽  
Chuping Zheng ◽  
Yanyu Liu ◽  
Fangling Le ◽  
Fang Yang ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
G Quadruplex

Anticancer activity of novel ruthenium complex with 1,10-phenanthrolineselenazole as potent telomeric G-quadruplex inhibitor

2012 ◽  
Vol 20 ◽  
pp. 142-146 ◽  
Author(s):  
Qian Li ◽  
Dongdong Sun ◽  
Yanhui Zhou ◽  
Du Liu ◽  
Qianling Zhang ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Ruthenium Complex ◽  
G Quadruplex

Enhancement Effect of Zn-Arsenazo III Complex for G-quadruplex DNA Stability of Proto-oncogene Promoter Telomeres

2020 ◽  
Vol 17 (7) ◽  
pp. 858-866
Author(s):  
Liyuan Zou ◽  
Hongbo Li ◽  
Mingbin Liu ◽  
Weihua Zhao ◽  
Suqin Wang
Keyword(s):  
Enhancement Effect ◽  
Antitumor Therapy ◽  
Quadruplex Dna ◽  
G Quadruplex ◽  
Cellular Context ◽  
Different Temperatures ◽  
Nucleic Acid Stain ◽  
Reciprocal Method ◽  
Growth Of Tumor ◽  
Stabilizing Ligands

Background: Controlling the structure of proto-oncogene telomeres is very important in antitumor therapy. There are relationships between G-quadruplex DNA and the growth of tumor cell. Methods: In this study, spectroscopic, cyclic voltammetry and viscosity methods were employed to investigate the interaction between Zn-Arsenazo Ⅲ complex and G-quadruplex DNA by using 4S Green Plus Nucleic Acid Stain as a spectral probe in PBS buffer. The binding ratios were n Arsenazo Ⅲ : n Zn(Ⅱ) = 5:1 for Zn-Arsenazo Ⅲ complex and n Zn- Arsenazo Ⅲ : n G-quadruplex DNA = 8:1 for Zn-Arsenazo Ⅲ-G-quadruplex DNA. The bonding constants (Kθ 298.15K=4.44x105 L·mol-1, Kθ 308.15K= 1.00x105 L·mol-1, Kθ 318.15K= 1.04x106 L·mol-1) were obtained by double reciprocal method at different temperatures, Which was found that the interaction between Zn-Arsenazo Ⅲ complex and Gquadruplex DNA was driven by enthalpy. Furthermore, the research further confirmed that the interaction mode between Zn-Arsenazo Ⅲ complex and G-quadruplex DNA was a mixed binding which involved intercalation and non-intercalation interaction. Results and Conclusion: Together these findings also have corroborated the application of stabilizing ligands and intervening with their function for target G-quadruplexes in a cellular context.

scholarly journals Anticancer Activity and Cellular Repression of c-MYC by the G-Quadruplex-Stabilizing 11-Piperazinylquindoline Is Not Dependent on Direct Targeting of the G-Quadruplex in the c-MYC Promoter

2012 ◽  
Vol 55 (13) ◽  
pp. 6076-6086 ◽  
Author(s):  
Peda V. L. Boddupally ◽  
Seongmin Hahn ◽  
Cristina Beman ◽  
Biswanath De ◽  
Tracy A. Brooks ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
G Quadruplex ◽  
Direct Targeting

scholarly journals Xanthene and Xanthone Derivatives as G-Quadruplex Stabilizing Ligands

Molecules ◽  
2013 ◽  
Vol 18 (11) ◽  
pp. 13446-13470 ◽  
Author(s):  
Alessandro Altieri ◽  
Antonello Alvino ◽  
Stephan Ohnmacht ◽  
Giancarlo Ortaggi ◽  
Stephen Neidle ◽  
...  
Keyword(s):  
Xanthone Derivatives ◽  
G Quadruplex ◽  
Stabilizing Ligands

Tetramethylpyridiniumporphyrazines — A New Class of G-Quadruplex Inducing and Stabilizing Ligands.

ChemInform ◽  
2007 ◽  
Vol 38 (10) ◽  
Author(s):  
Diana P. N. Goncalves ◽  
Raphael Rodriguez ◽  
Shankar Balasubramanian ◽  
Jeremy K. M. Sanders
Keyword(s):  
New Class ◽  
G Quadruplex ◽  
Stabilizing Ligands
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