Natural products have served as a rich source of 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 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 complexing 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.
International journal of pharmaceutics. 2016 Jul 06 [Epub ahead of print]
Tahsin F Kellici, Maria V Chatziathanasiadou, Dimitris Diamantis, Alexandra Chatzikonstantinou, Ioannis Andreadelis, Eirini Christodoulou, Georgia Valsami, Thomas Mavromoustakos, Andreas G Tzakos
Department of Chemistry, University of Ioannina, Ioannina 45110, Greece; Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis Zografou 15771, Greece., Department of Chemistry, University of Ioannina, Ioannina 45110, Greece., Department of Chemistry, University of Ioannina, Ioannina 45110, Greece., Department of Chemistry, University of Ioannina, Ioannina 45110, Greece., Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis Zografou 15771, Greece., Department of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis Zografou 15771, Greece., Department of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis Zografou 15771, Greece., Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis Zografou 15771, Greece., Department of Chemistry, University of Ioannina, Ioannina 45110, Greece. Electronic address: .