Design and synthesis of unsymmetric macrocyclic hexaoxazole compounds with an ability to induce distinct G-quadruplex topologies in telomeric DNA

2016 ◽  
Vol 14 (22) ◽  
pp. 5109-5116 ◽  
Author(s):  
Mai Sakuma ◽  
Yue Ma ◽  
Yamato Tsushima ◽  
Keisuke Iida ◽  
Takatsugu Hirokawa ◽  
...  
Keyword(s):  
Ring System ◽  
Side Chains ◽  
Telomeric Dna ◽  
Macrocyclic Ring ◽  
Design And Synthesis ◽  
G Quadruplex

New macrocyclic hexaoxazole compounds bearing two side chains on an unsymmetrical macrocyclic ring system,i.e., 4,2-L2H2-6OTD (2) and 5,1-L2H2-6OTD (3), were designed as candidate G-quadruplex (G4) ligands and synthesized.

Design and Synthesis of G-Quadruplex Ligands Bearing Macrocyclic Hexaoxazoles with Four-Way Side Chains

Heterocycles ◽  
2012 ◽  
Vol 84 (1) ◽  
pp. 401 ◽  
Author(s):  
Kazuo Nagasawa ◽  
Keisuke Iida ◽  
Satoki Majima ◽  
Terumi Ohtake ◽  
Masayuki Tera ◽  
...  
Keyword(s):  
Side Chains ◽  
Design And Synthesis ◽  
G Quadruplex

scholarly journals Rational Design and Synthesis of Naphthalene Diimide Linked Bis-Naphthalimides as DNA Interactive Agents

2021 ◽  
Vol 9 ◽  
Author(s):  
M. Shaheer Malik ◽  
Syed Farooq Adil ◽  
Ziad Moussa ◽  
Hatem M. Altass ◽  
Ismail I. Althagafi ◽  
...  
Keyword(s):  
Rational Design ◽  
Thermal Denaturation ◽  
Telomeric Dna ◽  
Docking Analysis ◽  
Design And Synthesis ◽  
Naphthalene Diimide ◽  
G Quadruplex ◽  
Further Development ◽  
Molecular Docking Analysis ◽  
Better Than

A molecular modeling assisted rational design and synthesis of naphthalene diimide linked bis-naphthalimides as potential DNA interactive agents is described. Chemical templates incorporating naphthalene diimide as a linker in bis-naphthalimide motif were subjected to molecular docking analysis at specific intercalation and telomeric DNA G-quadruplex sites. Excellent results were obtained, which were better than the standards. A short and convenient synthetic route was employed to access these hybrids experimentally, followed by evaluation of their ability to cause thermal denaturation of DNA and cytotoxic properties along with ADME predictions. The obtained results provided useful insights and two potential molecules were identified for further development.

scholarly journals PhenQE8, a Novel Ligand of the Human Telomeric Quadruplex

2021 ◽  
Vol 22 (2) ◽  
pp. 749
Author(s):  
Patricia B. Gratal ◽  
Julia G. Quero ◽  
Adrián Pérez-Redondo ◽  
Zoila Gándara ◽  
Lourdes Gude
Keyword(s):  
Equilibrium Dialysis ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
The Novel ◽  
X Ray Diffraction ◽  
Telomeric Dna ◽  
Healthy Human ◽  
Quadruplex Dna ◽  
Step Procedure ◽  
G Quadruplex

A novel quadruplex ligand based on 1,10-phenanthroline and incorporating two guanyl hydrazone functionalities, PhenQE8, is reported herein. Synthetic access was gained in a two-step procedure with an overall yield of 61%. X-ray diffraction studies revealed that PhenQE8 can adopt an extended conformation that may be optimal to favor recognition of quadruplex DNA. DNA interactions with polymorphic G-quadruplex telomeric structures were studied by different techniques, such as Fluorescence resonance energy transfer (FRET) DNA melting assays, circular dichroism and equilibrium dialysis. Our results reveal that the novel ligand PhenQE8 can efficiently recognize the hybrid quadruplex structures of the human telomeric DNA, with high binding affinity and quadruplex/duplex selectivity. Moreover, the compound shows significant cytotoxic activity against a selected panel of cultured tumor cells (PC-3, HeLa and MCF-7), whereas its cytotoxicity is considerably lower in healthy human cells (HFF-1 and RPWE-1).

Research Progress in the Typical Structure of Human Telomeric G-Quadruplex

2014 ◽  
Vol 955-959 ◽  
pp. 419-422
Author(s):  
Gui Lin Liu ◽  
Yan Ping Ding ◽  
Yan Ling Wu ◽  
Wen Zhang
Keyword(s):  
Cell Cycle ◽  
Dna Sequences ◽  
Research Progress ◽  
Human Chromosomes ◽  
Telomeric Dna ◽  
Typical Structure ◽  
Special Sequence ◽  
Physiological Processes ◽  
G Quadruplex ◽  
Small Molecule Ligands

Telomeric DNA of human chromosomes plays a significant role in physiological processes such as cell cycle, aging, cancer and genetic stability due to its special sequence and structure. The research on small molecule ligands targeting G-quadruplex formed by such special sequence has attracted considerable attention, and has achieved great breakthrough. In this paper, we summarize the DNA sequences and structures of three kinds of typical human telomeric G-quadruplex, providing an important reference for further research.

Design and Synthesis of an Expanded Porphyrin That Has Selectivity for the c-MYC G-Quadruplex Structure

2005 ◽  
Vol 127 (9) ◽  
pp. 2944-2959 ◽  
Author(s):  
Jeyaprakashnarayanan Seenisamy ◽  
Sridevi Bashyam ◽  
Vijay Gokhale ◽  
Hariprasad Vankayalapati ◽  
Daekyu Sun ◽  
...  
Keyword(s):  
Design And Synthesis ◽  
Quadruplex Structure ◽  
G Quadruplex ◽  
Expanded Porphyrin

Aggregation Behavior of a Six‐Membered Cyclic Frustrated Phosphane/Borane Lewis Pair: Formation of a Supramolecular Cyclooctameric Macrocyclic Ring System

2019 ◽  
Vol 58 (3) ◽  
pp. 882-886 ◽  
Author(s):  
Xiaoming Jie ◽  
Constantin G. Daniliuc ◽  
Robert Knitsch ◽  
Michael Ryan Hansen ◽  
Hellmut Eckert ◽  
...  
Keyword(s):  
Pair Formation ◽  
Ring System ◽  
Aggregation Behavior ◽  
Macrocyclic Ring

scholarly journals Telomeric G-Quadruplexes: From Human to Tetrahymena Repeats

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Erika Demkovičová ◽  
Ľuboš Bauer ◽  
Petra Krafčíková ◽  
Katarína Tlučková ◽  
Petra Tóthova ◽  
...  
Keyword(s):  
Life Cycle ◽  
Base Substitution ◽  
Telomeric Dna ◽  
Purine Base ◽  
Telomeric Sequences ◽  
G Quadruplex ◽  
The Stability ◽  
Scientific Value ◽  
The Relationship ◽  
Adenine Base

The human telomeric and protozoal telomeric sequences differ only in one purine base in their repeats; TTAGGG in telomeric sequences; and TTGGGG in protozoal sequences. In this study, the relationship between G-quadruplexes formed from these repeats and their derivatives is analyzed and compared. The human telomeric DNA sequence G3(T2AG3)3 and related sequences in which each adenine base has been systematically replaced by a guanine were investigated; the result is Tetrahymena repeats. The substitution does not affect the formation of G-quadruplexes but may cause differences in topology. The results also show that the stability of the substituted derivatives increased in sequences with greater number of substitutions. In addition, most of the sequences containing imperfections in repeats which were analyzed in this study also occur in human and Tetrahymena genomes. Generally, the presence of G-quadruplex structures in any organism is a source of limitations during the life cycle. Therefore, a fuller understanding of the influence of base substitution on the structural variability of G-quadruplexes would be of considerable scientific value.

scholarly journals The role of side chains in the interaction of new antitumor pyrimidoacridinetriones with DNA: molecular dynamics simulations.

2000 ◽  
Vol 47 (1) ◽  
pp. 47-57 ◽  
Author(s):  
J Mazerski ◽  
I Antonini ◽  
S Martelli
Keyword(s):  
Molecular Dynamics ◽  
Rational Design ◽  
Md Simulations ◽  
Ring System ◽  
Side Chain ◽  
Side Chains ◽  
Intercalation Complex ◽  
Highly Active ◽  
Simulation Techniques ◽  
Dynamics Simulations

Pyrimidoacridinetriones (PATs) are a new group of highly active antitumor compounds. It seems reasonable to assume that, like for some other acridine derivatives, intercalation into DNA is a necessary, however not a sufficient condition for antitumor activity of these compounds. Rational design of new compounds of this chemotype requires knowledge about the structure of the intercalation complex, as well as about interactions responsible for its stability. Computer simulation techniques such as molecular dynamics (MD) may provide valuable information about these problems. The results of MD simulations performed for three rationally selected PATs are presented in this paper. The compounds differ in the number and position of side chains. Each of the compounds was simulated in two systems: i) in water, and ii) in the intercalation complex with the dodecamer duplex d(GCGCGCGCGCGC)2. The orientation of the side chain in relation to the ring system is determined by the position of its attachment. Orientation of the ring system inside the intercalation cavity depends on the number and position of side chain(s). The conformations of the side chain(s) of all PATs studied in the intercalation complex were found to be very similar to those observed in water.

scholarly journals Selective Interactions with Various G-Quadruplex DNA Forming Sequences by Berberine and Palmatine Analogues

2018 ◽  
Author(s):  
Marco Franceschin ◽  
Lorenzo Cianni ◽  
Massimo Pitorri ◽  
Emanuela Micheli ◽  
Stefano Cacchione ◽  
...  
Keyword(s):  
Anticancer Drugs ◽  
Natural Compounds ◽  
Side Chains ◽  
Quadruplex Dna ◽  
G Quadruplex ◽  
Quadruplex Formation ◽  
Selective Interactions

In this article/review, the selective interactions of several berberine and palmatine derivatives with various DNA G-quadruplex structures are reported. These derivatives were constructed starting from two natural compounds, berberine and palamatine, through specific synthetic passages following two different schemes for each of them and using several substituents. The details of these synthesis are also described. Indeed, the study of the interactions of these derivative compounds with various G-quadruplex forming sequences was carried out by means of various structural and biochemical techniques. The results show that the presence of suitable side chains are very useful to improve the interaction of the ligands with G-quadruplex structures. Thus, since G-quadruplex formation is promoted by these compounds, which have never been reported before, these may be tested as potential anticancer drugs.

scholarly journals The Interaction of Telomeric DNA and C-myc22 G-Quadruplex with 11 Natural Alkaloids

2012 ◽  
Vol 22 (2) ◽  
pp. 127-136 ◽  
Author(s):  
Xiaohui Ji ◽  
Hongxia Sun ◽  
Huaxi Zhou ◽  
Junfeng Xiang ◽  
Yalin Tang ◽  
...  
Keyword(s):  
Telomeric Dna ◽  
G Quadruplex
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