scholarly journals Alkaloid Escholidine and Its Interaction with DNA Structures

Biology ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1225
Author(s):  
Petra Jarošová ◽  
Pavel Hannig ◽  
Kateřina Kolková ◽  
Stefania Mazzini ◽  
Eva Táborská ◽  
...  

Berberine, the most known quaternary protoberberine alkaloid (QPA), has been reported to inhibit the SIK3 protein connected with breast cancer. Berberine also appears to reduce the bcl-2 and XIAP expression-proteins responsible for the inhibition of apoptosis. As some problems in the therapy with berberine arose, we studied the DNA binding properties of escholidine, another QPA alkaloid. CD, fluorescence, and NMR examined models of i-motif and G-quadruplex sequences present in the n-myc gene and the c-kit gene. We provide evidence that escholidine does not induce stabilization of the i-motif sequences, while the interaction with G-quadruplex structures appears to be more significant.

2021 ◽  
Vol 22 (12) ◽  
pp. 6476
Author(s):  
Sabrina Dallavalle ◽  
Luce M. Mattio ◽  
Roberto Artali ◽  
Loana Musso ◽  
Anna Aviñó ◽  
...  

Curaxins and especially the second-generation derivative curaxin CBL0137 have important antitumor activities in multiple cancers such as glioblastoma, melanoma and others. Although most of the authors suggest that their mechanism of action comes from the activation of p53 and inactivation of NF-kB by targeting FACT, there is evidence supporting the involvement of DNA binding in their antitumor activity. In this work, the DNA binding properties of curaxin CBL0137 with model quadruplex DNA oligomers were studied by 1H NMR, CD, fluorescence and molecular modeling. We provided molecular details of the interaction of curaxin with two G-quadruplex structures, the single repeat of human telomere d(TTAGGGT)4 and the c-myc promoter Pu22 sequence. We also performed 1H and 31P NMR experiments were also performed in order to investigate the interaction with duplex DNA models. Our data support the hypothesis that the interaction of curaxin with G-quadruplex may provide a novel insight into the DNA-binding properties of CBL0137, and it will be helpful for the design of novel selective DNA-targeting curaxin analogues.


2020 ◽  
Vol 49 (30) ◽  
pp. 10360-10379 ◽  
Author(s):  
Son Q. T. Pham ◽  
Christopher Richardson ◽  
Celine Kelso ◽  
Anthony C. Willis ◽  
Stephen F. Ralph

Changing the position of pendant groups on nickel Schiff base complexes can alter their binding behaviour towards quadruplex DNA.


1989 ◽  
Vol 264 (31) ◽  
pp. 18433-18439 ◽  
Author(s):  
F R Taylor ◽  
E P Shown ◽  
E B Thompson ◽  
A A Kandutsch

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sabrina Dallavalle ◽  
Loana Musso ◽  
Roberto Artali ◽  
Anna Aviñó ◽  
Leonardo Scaglioni ◽  
...  

AbstractPoly ADP-ribose polymerases (PARP) are key proteins involved in DNA repair, maintenance as well as regulation of programmed cell death. For this reason they are important therapeutic targets for cancer treatment. Recent studies have revealed a close interplay between PARP1 recruitment and G-quadruplex stabilization, showing that PARP enzymes are activated upon treatment with a G4 ligand. In this work the DNA binding properties of a PARP-1 inhibitor derived from 7-azaindole-1-carboxamide, (2-[6-(4-pyrrolidin-1-ylmethyl-phenyl)-pyrrolo[2,3-b]pyridin-1-yl]-acetamide, compound 1) with model duplex and quadruplex DNA oligomers were studied by NMR, CD, fluorescence and molecular modelling. We provide evidence that compound 1 is a strong G-quadruplex binder. In addition we provide molecular details of the interaction of compound 1 with two model G-quadruplex structures: the single repeat of human telomeres, d(TTAGGGT)4, and the c-MYC promoter Pu22 sequence. The formation of defined and strong complexes with G-quadruplex models suggests a dual G4 stabilization/PARP inhibition mechanism of action for compound 1 and provides the molecular bases of its therapeutic potential.


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