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Interaction of dpyatriz and Cu/Zn-dpyatriz complexes with human telomere DNA: The role of G-quadruplex formation and its effect on antitumor and antitelomerase activity

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Title Interaction of dpyatriz and Cu/Zn-dpyatriz complexes with human telomere DNA: The role of G-quadruplex formation and its effect on antitumor and antitelomerase activity
 
Creator Renuga, Duraisamy
Maheswari, Palanisamy Uma
Begum, K.M. Meera Sheriffa
 
Subject G-quadruplex
Triazine
Dipyridyl amine
Antitelomerase
Anticancer
Human telomere
 
Description 217-229
1,3,5-Triazine derivative of dipyridyl amine (dpyatriz) and the Cu(II), Zn(II) complexes have been prepared,
characterized by CHN, IR, NMR and mass measurements and interacted with HTelo8 and HTelo20, the two types of human
telomere repeat DNA (TTAGGG)n; n = 8, 20. The telomere DNAs have been treated with all three compounds (dpyatriz,
Cu-dpyatriz and Zn-dpyatriz) under parallel/antiparallel and random coiled conditions. The interactions are followed by
circular dichrosim measurements, fluorescent intercalator displacement (FID) assays and molecular docking studies through
MOE program. The free ligand and its Cu(II) and Zn(II) complexes stabilize predominantly antiparallel G-quadruplex form
under antiparallel and no salt conditions. The binding constant (Kb) values calculated for the ligand and complexes are in the
range of 1.9 x 105 M-1 to 4.2 x 107 M-1 under various conditions show the higher affinity of G-quadruplex conformations.
The FID assay using thiazole orange with HTelo20 clearly depicts the G-quadruplex stabilization through strong binding
mode. Also, all the three compounds dpyatriz, Cu-dpyatriz and Zn-dpyatriz show an intercalative mode of interaction with
antiparallel G quadruplex DNA in molecular docking studies. The compounds show cytotoxicity with the IC50 values in the
range of 50 – 90 nM, and antitelomerase activity in the range of 5 to 10 μM.
 
Date 2023-03-17T07:28:22Z
2023-03-17T07:28:22Z
2023-03
 
Type Article
 
Identifier 2583-1321 (Online); 0019-5103 (Print)
http://nopr.niscpr.res.in/handle/123456789/61541
https://doi.org/10.56042/ijc.v62i3.71998
 
Language en
 
Publisher NIScPR-CSIR,India
 
Source IJC Vol.62(03) [Mar 2023]