Synthesis of 10-O-aryl-substituted berberine derivatives by Chan–Evans–Lam coupling and investigation of their DNA-binding properties

• Peter Jonas Wickhorst,
• Mathilda Blachnik,
• Denisa Lagumdzija and
• Heiko Ihmels

Beilstein J. Org. Chem. 2021, 17, 991–1000, doi:10.3762/bjoc.17.81

• , specifically 13- and 9-substituted berberine derivatives have gained much interest as selective DNA ligands that specifically target quadruplex DNA (G4-DNA) [23][24][25][26][27][28][29], i.e., non-canonical, biologically relevant DNA structures that are formed by the association of four guanine-rich DNA

• berberrubine. And herein, we report the application of this Cu-mediated coupling reaction for the synthesis of 10-O-arylated berberine derivatives as unexpected reaction product, along with first experiments that demonstrate the G4-DNA-binding properties of this class of berberine derivatives. Results and

• ) process from the electron-rich benzodioxole unit to the isoquinolinium [44], which also contributes to the low fluorescence intensity of derivatives 5a–e. DNA-binding properties Thermal DNA denaturation experiments For a first screening of the interactions of the derivatives 5a–e with different G4-DNA

Synthesis and investigation of quadruplex-DNA-binding, 9-O-substituted berberine derivatives

• Jonas Becher,
• Daria V. Berdnikova,
• Heiko Ihmels and
• Christopher Stremmel

Beilstein J. Org. Chem. 2020, 16, 2795–2806, doi:10.3762/bjoc.16.230

• derivatives. Notably, a clear relationship between the binding affinity of the ligands with the length of the alkyl linker chain, n, was not observed. However, depending on the structure, the ligands exhibited different effects when bound to the G4-DNA, such as fluorescent light-up effects and formation of

• ICD bands, which are mostly pronounced with a linker length of n = 4 (with a2) and n = 5 (with 22AG), thus indicating that each ligand–G4-DNA complex has a specific structure with respect to relative alignment and conformational flexibility of the ligand in the binding site. It was shown exemplarily

• with one representative ligand from the series that such berberine–adenine conjugates exhibit a selective binding, specifically a selectivity to quadruplex DNA in competition with duplex DNA, and a preferential thermal stabilization of the G4-DNA forms 22AG and KRAS. Notably, the experimental data do

Identification of optimal fluorescent probes for G-quadruplex nucleic acids through systematic exploration of mono- and distyryl dye libraries

• Xiao Xie,
• Michela Zuffo,
• Marie-Paule Teulade-Fichou and
• Anton Granzhan

Beilstein J. Org. Chem. 2019, 15, 1872–1889, doi:10.3762/bjoc.15.183

• cationic dyes was synthesized and investigated with respect to their optical properties, propensity to aggregation in aqueous medium, and capacity to serve as fluorescence “light-up” probes for G-quadruplex (G4) DNA and RNA structures. Among the 61 compounds, 57 dyes showed preferential enhancement of

• fluorescence intensity in the presence of one or another G4-DNA or RNA structure, while no dye displayed preferential response to double-stranded DNA or single-stranded RNA analytes employed at equivalent nucleotide concentration. Thus, preferential fluorimetric response towards G4 structures appears to be a

• rapid topological classification of G4-DNA structures. Keywords: fluorescent probes; G-quadruplex DNA; G-quadruplex RNA; nucleic acids; styryl dyes; Introduction Development of fluorescent probes for G-quadruplex (G4) DNA and RNA is an active research area. In fact, these non-canonical nucleic acid

Synthesis of 9-arylalkynyl- and 9-aryl-substituted benzo[b]quinolizinium derivatives by Palladium-mediated cross-coupling reactions

• Siva Sankar Murthy Bandaru,
• Darinka Dzubiel,
• Heiko Ihmels,
• Mohebodin Karbasiyoun,
• Mohamed M. A. Mahmoud and
• Carola Schulzke

Beilstein J. Org. Chem. 2018, 14, 1871–1884, doi:10.3762/bjoc.14.161

• topoisomerase inhibitors [5]. More recently, much interest in this research area is focused on the non-canonical quadruplex DNA (G4-DNA) [6][7][8]. Mostly based on the principles and requirements of ligands that bind to duplex DNA, numerous G4-DNA ligands have been developed to study their selectivity and

• binding properties towards G4-DNA because of the biological importance of G4-DNA [9][10][11][12][13]. Along these lines, we and others have established the class of annelated quinolizinium derivatives as versatile ligands that bind to duplex, triplex and quadruplex DNA depending on their shape and size

• ]quinolizinium derivatives with a large extension of the π-system, which should provide promising properties as G4-DNA ligands, we also focused our attention on the Sonogashira reaction as synthetic route to arylalkynyl-substituted derivatives. In this case, we aimed at donor-substituted derivatives such as 2b–d

Synthesis of bi- and bis-1,2,3-triazoles by copper-catalyzed Huisgen cycloaddition: A family of valuable products by click chemistry

• Zhan-Jiang Zheng,
• Ding Wang,
• Zheng Xu and
• Li-Wen Xu

Beilstein J. Org. Chem. 2015, 11, 2557–2576, doi:10.3762/bjoc.11.276

• corresponding primary guanidine or diisopropylguanidine analogs (60 and 61, Scheme 20) [40], which could be used as potential G4 DNA ligands with high selectivity over duplexed DNA. Similar to the above strategies or methods, a number of researchers have developed various dialkyne substrates with varied spacers