title: Solution and Solid-State Analysis of Binding of 13-Substituted Berberine Analogues to Human Telomeric G-quadruplexes.
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.
authors: Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019, Sesto Fiorentino, FI, Italy.
authors: Marta
authors: M
authors: Ferraroni
authors: Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019, Sesto Fiorentino, FI, Italy. carla.bazzicalupi@unifi.it.
authors: Carla
authors: C
authors: Bazzicalupi
authors: Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019, Sesto Fiorentino, FI, Italy.|Department NEUROFARBA-Pharmaceutical and nutraceutical section, Laboratory of Molecular Modeling Cheminformatics&QSAR, University of Firenze, via Ugo Schiff 6, 50019, Sesto Fiorentino, Firenze, Italy.
authors: Francesco
authors: F
authors: Papi
authors: Naxospharma srl, via G. Di Vittorio, 70, 20026, Novate Milanese, Italy.
authors: Gaetano
authors: G
authors: Fiorillo
authors: Universidad Técnica Particular de Loja, Departamento de Ciencias de la Salud, San Cayetano Alto, Calle Paris, 1101608, Loja, Ecuador.|Istituto di Genetica Molecolare del CNR, Via Abbiategrasso 207, 27100, Pavia, Italy.
authors: Luis Miguel
authors: LM
authors: Guamán-Ortiz
authors: Department NEUROFARBA-Pharmaceutical and nutraceutical section, Laboratory of Molecular Modeling Cheminformatics&QSAR, University of Firenze, via Ugo Schiff 6, 50019, Sesto Fiorentino, Firenze, Italy.
authors: Alessio
authors: A
authors: Nocentini
authors: Istituto di Genetica Molecolare del CNR, Via Abbiategrasso 207, 27100, Pavia, Italy.
authors: Anna Ivana
authors: AI
authors: Scovassi
authors: Naxospharma srl, via G. Di Vittorio, 70, 20026, Novate Milanese, Italy.
authors: Paolo
authors: P
authors: Lombardi
authors: 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.
authors: Paola
authors: http://orcid.org/0000-0002-9137-2509
authors: P
authors: Gratteri
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001599:Berberine / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D054856:G-Quadruplexes; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D012996:Solutions; D013329:Structure-Activity Relationship; D016615:Telomere / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D008024:Ligands; D012996:Solutions; D001599:Berberine
keywords: G-quadruplexes; X-ray diffraction; alkaloids; berberine; crystal structure; telomeric DNA