Alkaloid Escholidine and Its Interaction with DNA Structures
Department of Chemistry, Faculty of Science, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic
Department of Food, Environmental and Nutritional Sciences (DEFENS), Section of Chemical and Biomolecular Sciences, University of Milan, Via Celoria 2, 20133 Milan, Italy
Department of Biochemistry, Faculty of Medicine, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic
Department of Chemical Engineering and Analytical Chemistry, University of Barcelona, Marti i Franquès 1, E-08028 Barcelona, Spain
Scientia Advice di Roberto Artali, 20832 Desio, Italy
Author to whom correspondence should be addressed.
Academic Editor: Weiguo Cao
Received: 6 September 2021
Revised: 18 November 2021
Accepted: 20 November 2021
Published: 24 November 2021
Escholidine is a rare protoberberine alkaloid present in trace amounts in roots of Eschscholtzia californica and in the aerial parts of Hunnemannia fumariaefolia. Due to the characteristic charged structure, it can interact with various forms of nucleic acids, including non-canonical structures. A series of spectroscopic experiments have shown notable melting stabilization of antiparallel G-quadruplex sequence DL40 induced by escholidine (ΔTm = 5.2 °C). Interaction stoichiometry calculated from fluorescence titration curves was estimated to be 4:1 or 5:1 (alkaloid:DNA). Nuclear Magnetic Resonance (NMR) experiments have confirmed that an external loop binding is likely responsible for this stabilization. The three-dimensional model of the complex between escholidine and DL40, obtained as a result of the molecular docking experiment, implies the preferred orientation of escholidine to the quadruplex structure. Since the stabilization of telomeric G-quadruplex structures by small ligands is often used as a strategy in anti-cancer therapy, alkaloid escholidine seems to be an interesting agent from a medicinal point of view.