title: Mapping the interactions and bioactivity of quercetin-(2-hydroxypropyl)-β-cyclodextrin complex.
abstract: Natural products have served as a rich source for drug discovery and development. In the last decade their fruitful integration in the drug discovery pipeline declined due to their reduced bioavailability, mainly attributed to their poor aqueous solubility. We synthesized a quercetin (QUE)-(2-hydroxypropyl)-β-cyclodextrin (HP-β-CD) complex that enabled amplification of its solubility and in the same time retained its bioactivity in T24 human bladder cancer cell line. The stability of the complex and the molecular basis of the interactions developed in this host-guest complex were assayed by incorporating an array of analytical techniques and Molecular Dynamics (MD) experiments. 2D DOSY NMR experiment revealed that the diffusion coefficient of free HP-β-CD was 3.55×10(-10)m(2)s(-1) while that of QUE-HP-β-CD inclusion complex 3.09×10(-10)m(2)s(-1), indicating the formation of a complex. Solid and liquid high resolution NMR spectroscopy data showed that the most pronounced differences in chemical shifts at carbons and protons correspondingly during complexation occur in the aromatic ring Α (bearing the two phenolic hydroxyl groups meta to each other). The chemical shift differences in the aromatic ring Β (bearing the two phenolic hydroxyl groups ortho to each other) were less pronounced. The MD results confirmed the experimental data.
authors.affiliation: Department of Chemistry, University of Ioannina, Ioannina 45110, Greece; Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis Zografou 15771, Greece.
authors.forename: Tahsin F
authors.initials: TF
authors.lastname: Kellici
authors.affiliation: Department of Chemistry, University of Ioannina, Ioannina 45110, Greece.
authors.forename: Maria V
authors.initials: MV
authors.lastname: Chatziathanasiadou
authors.affiliation: Department of Chemistry, University of Ioannina, Ioannina 45110, Greece.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Diamantis
authors.affiliation: Department of Chemistry, University of Ioannina, Ioannina 45110, Greece.
authors.forename: Alexandra V
authors.initials: AV
authors.lastname: Chatzikonstantinou
authors.affiliation: Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis Zografou 15771, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Andreadelis
authors.affiliation: Department of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis Zografou 15771, Greece.
authors.forename: Eirini
authors.initials: E
authors.lastname: Christodoulou
authors.affiliation: Department of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis Zografou 15771, Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Valsami
authors.affiliation: Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis Zografou 15771, Greece.
authors.forename: Thomas
authors.initials: T
authors.lastname: Mavromoustakos
authors.affiliation: Department of Chemistry, University of Ioannina, Ioannina 45110, Greece. Electronic address: agtzakos@gmail.com.
authors.forename: Andreas G
authors.initials: AG
authors.lastname: Tzakos
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D045744:Cell Line, Tumor; D004338:Drug Combinations; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D011794:Quercetin / Q000737:chemistry* / Q000378:metabolism*; D047392:beta-Cyclodextrins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D004338:Drug Combinations; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D011794:Quercetin
keywords: 2-Hydroxypropyl-cyclodextrin; Confocal microscopy; MTT assay; Molecular dynamics; Quercetin; Solid state NMR; UV spectroscopy