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. 2021 Nov 24;10(12):1225.
doi: 10.3390/biology10121225.

Alkaloid Escholidine and Its Interaction with DNA Structures

Petra Jarošová  1 , Pavel Hannig  1 , Kateřina Kolková  1 , Stefania Mazzini  2 , Eva Táborská  3 , Raimundo Gargallo  4 , Gigliola Borgonovo  2 , Roberto Artali  5 , Petr Táborský  1
Affiliations

Alkaloid Escholidine and Its Interaction with DNA Structures

Petra Jarošová et al. Biology (Basel). .

Abstract

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.

Keywords: DNA; G-quadruplex; alkaloid; cancer; escholidine; spectroscopy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structure of alkaloid escholidine.
Figure 2
Figure 2
G-tetrad (a) and three-dimensional schematic structure with potassium ions (b), unimolecular (c), bimolecular, (d) tetramolecular, and (e) G-quadruplex.
Figure 3
Figure 3
Primary (left) and secondary (right) structure of i-motif.
Figure 4
Figure 4
pH 5: CD spectra of 22nt (a), nmyc01 (b), and nmyc01m (c) in the absence (blue) and presence (red) of escholidine in acetic buffer (coligo = 2 µM, t = 20 °C). pH 7: CD spectra of GG1 (d), and DL40 (e), in the absence (blue) and presence (red) of escholidine at phosphate buffer (coligo = 2 µM, t = 20 °C). Temperature dependence: CD spectra recorded along with the melting experiment of nmyc01 (f), ellipticity trace measured at 287 nm (g), and the fraction of folded DNA calculated assuming an intramolecular two-step process (h).
Figure 5
Figure 5
Imino proton region of the 1D NMR titration spectra of nmyc01 (a), nmyc01m (b), and 22nt (c) at 25 °C and at different R = [drug]/[DNA] ratios. Imino protons (d) and aromatic protons (e) regions of the 1D NMR titration spectra of DL40 at 25 °C and different R = (drug)/(DNA) ratios. Imino protons region of the 1D NMR titration spectra of GG1 (f) and ckit21T12T21 (g) at 25 °C and different R = (drug)/(DNA) ratios.
Figure 6
Figure 6
Schematic representation of ckit21T12T21. Numbers refer to the position of bases within this sequence.
Figure 7
Figure 7
Side views of the complex between escholidine and the DL40 G-quadruplex, as obtained from the molecular docking experiment. The G-quadruplex target is contoured by a ghostly-white solvent accessible surface (SAS) and the nucleotides were depicted as filled rings: adenine in red, cytosine in yellow, guanine in green and thymine in blue. The escholidine alkaloid is represented as van der Waals (vdW) spheres and coloured according to the atom types. The drawing was created by using the Chimera-X software (Resource for Biocomputing, Visualization, and Informatics San Francisco, CA, USA) [63].
See this image and copyright information in PMC

References

    1. Rajecky M., Slaninova I., Mokrisova P., Urbanova J., Palkovsky M., Taborska E., Taborsky P. Alkaloid chelirubine and DNA: Blue and red luminescence. Talanta. 2013;105:317–319. doi: 10.1016/j.talanta.2012.10.045. - DOI - PubMed
    1. Rybakova S., Rajecky M., Urbanova J., Pencikova K., Taborska E., Gargallo R., Taborsky P. Interaction of oligonucleotides with benzo c phenanthridine alkaloid sanguilutine. Chem. Pap. 2013;67:568–572. doi: 10.2478/s11696-013-0340-x. - DOI
    1. Sandor R., Slanina J., Midlik A., Sebrlova K., Novotna L., Carnecka M., Slaninova I., Taborsky P., Taborska E., Pes O. Sanguinarine is reduced by NADH through a covalent adduct. Phytochemistry. 2018;145:77–84. doi: 10.1016/j.phytochem.2017.10.010. - DOI - PubMed
    1. Rajecky M., Sebrlova K., Mravec F., Taborsky P. Influence of Solvent Polarity and DNA-Binding on Spectral Properties of Quaternary Benzo c phenanthridine Alkaloids. PLoS ONE. 2015;10:e0129925. doi: 10.1371/journal.pone.0129925. - DOI - PMC - PubMed
    1. Leitao da-Cunha E.V., Fechine I.M., Guedes D.N., Barbosa-Filho J.M., Sobral da Silva M. Protoberberine Alkaloids. In: Cordell G.A., editor. The Alkaloids: Chemistry and Biology. Volume 62. Academic Press; Cambridge, MA, USA: 2005. pp. 1–75. - PubMed