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Chem Asian J. 2016 Apr 5;11(7):1107-15. doi: 10.1002/asia.201600116. Epub 2016 Mar 11.

Solution and Solid-State Analysis of Binding of 13-Substituted Berberine Analogues to Human Telomeric G-quadruplexes.

Author information

1
Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019, Sesto Fiorentino, FI, Italy.
2
Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019, Sesto Fiorentino, FI, Italy. carla.bazzicalupi@unifi.it.
3
Department NEUROFARBA-Pharmaceutical and nutraceutical section, Laboratory of Molecular Modeling Cheminformatics&QSAR, University of Firenze, via Ugo Schiff 6, 50019, Sesto Fiorentino, Firenze, Italy.
4
Naxospharma srl, via G. Di Vittorio, 70, 20026, Novate Milanese, Italy.
5
Universidad Técnica Particular de Loja, Departamento de Ciencias de la Salud, San Cayetano Alto, Calle Paris, 1101608, Loja, Ecuador.
6
Istituto di Genetica Molecolare del CNR, Via Abbiategrasso 207, 27100, Pavia, Italy.
7
Department NEUROFARBA-Pharmaceutical and nutraceutical section, Laboratory of Molecular Modeling Cheminformatics&QSAR, University of Firenze, via Ugo Schiff 6, 50019, Sesto Fiorentino, Firenze, Italy. paola.gratteri@unifi.it.

Abstract

The interaction between 13-phenylalkyl and 13-diphenylalkyl berberine derivatives (NAX) and human telomeric DNA G4 structures has been investigated by both spectroscopic and crystallographic methods. NAX042 and NAX053 are the best compounds improving the performance of the natural precursor berberine. This finding is in agreement with the X-ray diffraction result for the NAX053-Tel12 adduct, showing the ligand which interacts via π-stacking, sandwiched at the interface of two symmetry-related quadruplex units, with its benzhydryl group contributing to the overall stability of the adduct by means of additional π-stacking interactions with the DNA residues. The berberine derivatives were also investigated for their cytotoxic activity towards a panel of human cancer cell lines. Compounds NAX042 and NAX053 affect the viability of cancer cell lines in a dose-dependent manner.

KEYWORDS:

G-quadruplexes; X-ray diffraction; alkaloids; berberine; crystal structure; telomeric DNA

PMID:
26865223
DOI:
10.1002/asia.201600116
[Indexed for MEDLINE]

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