| 1. |
- Colas, Kilian, et al.
(author)
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Indolylbenzothiadiazoles as highly tunable fluorophores for imaging lipid droplet accumulation in astrocytes and glioblastoma cells
- 2021
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In: RSC Advances. - : Royal Society of Chemistry. - 2046-2069. ; 11:39, s. 23960-23967
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Journal article (peer-reviewed)abstract
- We present an extensive photophysical study of a series of fluorescent indolylbenzothiadiazole derivatives and their ability to specifically image lipid droplets in astrocytes and glioblastoma cells. All compounds in the series displayed positive solvatochromism together with large Stokes shifts, and π-extended derivatives exhibited elevated brightness. It was shown that the fluorescence properties were highly tunable by varying the electronic character or size of the N-substituent on the indole motif. Three compounds proved capable as probes for detecting small quantities of lipid deposits in healthy and cancerous brain cells. In addition, all twelve compounds in the series were predicted to cross the blood–brain barrier, which raises the prospect for future in vivo studies for exploring the role of lipid droplets in the central nervous system.
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| 2. |
- Doloczki, Susanne, et al.
(author)
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An Indolin-3-imine Photobase and pH Sensitive Fluorophore
- 2023
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In: ChemPhotoChem. - : John Wiley & Sons. - 2367-0932.
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Journal article (peer-reviewed)abstract
- This work presents the pH sensing ability of a fluorescent indolin-3-imine derivative. Protonation of the weakly basic imine (pKa = 8.3 of its conjugate acid) results in a significant redshift of the absorption band. The fluorophore acts as a photobase, with a basicity increase of approximately 6 units upon photoexcitation. This behavior promotes excited state proton transfer from weak acids such as protic solvents. The characteristics of the fluorophore enable sensing of water fractions in organic solvents and differentiation between methanol, ethanol, and longer chain alcohols. Initial cell studies indicated the future potential of indolin-3-imines as fluorophores for bioimaging applications.
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| 3. |
- Doloczki, Susanne, et al.
(author)
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Photoinduced ring‐opening and phototoxicity of an indolin‐3‐one derivative
- 2023
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In: Chemistry - A European Journal. - : John Wiley & Sons. - 0947-6539 .- 1521-3765. ; 29:51
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Journal article (peer-reviewed)abstract
- The study of a fluorescent indolin-3-one derivative is reported that, as opposed to its previously described congeners, selectively undergoes photoactivated ring-opening in apolar solvents. The excited state involved in this photoisomerization was partially deactivated by the formation of singlet oxygen. Cell studies revealed lipid droplet accumulation and efficient light-induced cytotoxicity.
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| 4. |
- Doloczki, Susanne, et al.
(author)
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Photophysical characterization and fluorescence cell imaging applications of 4-N-substituted benzothiadiazoles
- 2022
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In: RSC Advances. - : Royal Society of Chemistry. - 2046-2069. ; 12:23, s. 14544-14550
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Journal article (peer-reviewed)abstract
- In this work, a series of fluorescent 2,1,3-benzothiadiazole derivatives with various N-substituents in the 4- position was synthesized and photophysically characterized in various solvents. Three compounds emerged as excellent fluorescent probes for imaging lipid droplets in cancer cells. A correlation between their high lipophilicity and lipid droplet specificity could be found, with log P ≥ 4 being characteristic for lipid droplet accumulation.
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| 5. |
- Dyrager, Christine, 1975, et al.
(author)
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2,6,8-Trisubstituted 3-hydroxychromone derivatives as fluorophores for live-cell imaging.
- 2009
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In: Chemistry (Weinheim an der Bergstrasse, Germany). - : Wiley. - 1521-3765 .- 0947-6539. ; 15:37, s. 9417-23
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Journal article (peer-reviewed)abstract
- We present the synthesis and photophysical characterisation of a series of structurally diverse, fluorescent 2,6,8-trisubstituted 3-hydroxychromone derivatives with high fluorescence quantum yields and molar extinction coefficients. Two of these derivatives (9 and 10 a) have been studied as fluorophores for cellular imaging in HeLa cells and show excellent permeability and promising fluorescence properties in a cellular environment. In addition, we have demonstrated by photophysical characterisation of 3-isobutyroxychromone derivatives that esterification of the 3-hydroxyl group results in acceptable and useful fluorescence properties.
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| 6. |
- Dyrager, Christine, 1975
(author)
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Design and Synthesis of Chalcone and Chromone Derivatives as Novel Anticancer Agents
- 2012
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Doctoral thesis (other academic/artistic)abstract
- This thesis comprises the design and synthesis of chalcone and chromone derivatives and their use in various biological applications, particularly as anticancer agents (targeting proteins associated with cancer pathogenesis) and as potential fluorophores for live-cell imaging. Conveniently, all structures presented were synthesized from commercially available 2 ́-hydroxyacetophenones. Different synthetic strategies were used to obtain an easily accessible chromone scaffold with appropriate handles that allows regioselective introduction of various substituents. Structural diversity was accomplished by using palladium-mediated reactions for the incorporation of suitable substituents for the generation of chromone derivatives that possess different biological activities. Challenging synthesis provided a series of fluorescent 2,6,8-trisubstituted 3- hydroxychromone derivatives with high quantum yields and molar extinction coefficients. Two of these derivatives were studied as fluorophores in live-cell imaging and showed rapid absorption, non-cytotoxic profiles and excellent fluorescent properties in a cellular environment. Synthetic chromone precursors, i.e. chalcones, and related dienones were evaluated as antiproliferative agents that interfere with the tubulin-microtubule equilibrium, crucial for cellular mitosis. It was shown that several of the synthesized compounds destabilize tubulin assembly. However, one of the compounds was instead found to stabilize tubulin to the same extent as the known anticancer drug docetaxel, thus representing the first chalcone with microtubule stabilizing activity. Molecular docking was used in order to theoretically investigate the interactions of the chalcones with ␣-tubulin mainly focusing on binding modes, potential interactions and specific binding sites. Structural-based design and extensive synthesis provided chromone-based derivatives that target two different MAP kinases (p38␣ and MEK1), involved in essential cellular signal transduction pathways. The study resulted in a series of highly selective ATP-competitive chromone-based p38␣ inhibitors with IC50 values in the nanomolar range. Among those, two derivatives also showed inhibition of p38 signaling in human breast cancer cells. Furthermore, molecular docking was used to study potential structural modifications on the chromone structure in order to obtain highly potent derivatives that selectively target the allosteric pocket on MEK1. Initial studies provided a first generation of non-ATP- competitive chromone derivatives that prevents the activation of MEK1 with micromolar activities.
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| 7. |
- Dyrager, Christine, 1975, et al.
(author)
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Design, synthesis, and biological evaluation of chromone-based p38 MAP kinase inhibitors
- 2011
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In: Journal of Medicinal Chemistry. ; 54, s. 7427-7431
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Journal article (peer-reviewed)abstract
- 3-(4-Fluorophenyl)-2-(4-pyridyl)chromone derivatives were synthesized and evaluated as p38 MAP kinase inhibitors. Introduction of an amino group in the 2-position of the pyridyl moiety gave p38α inhibitors with IC(50) in the low nanomolar range (e.g., IC(50) = 17 nm). The inhibitors showed excellent selectivity profiles when tested on a panel of 62 kinases, as well as efficient inhibition of p38 signaling in human breast cancer cells.
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| 8. |
- Dyrager, Christine, 1975, et al.
(author)
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Inhibitors and promoters of tubulin polymerization : Synthesis and biological evaluation of chalcones and related dienones as potential anticancer agents
- 2011
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In: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896 .- 1464-3391. ; 19:8, s. 2659-2665
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Journal article (peer-reviewed)abstract
- A series of dihalogenated chalcones and structurally related dienones were synthesized and evaluated for their antiproliferative activity in 10 different cancer cell lines and for their effect on microtubule assembly. All compounds showed cytotoxic activity, with IC50 values in the 5-280 mu M range depending on the chalcone structure and the cell line. Five of the compounds were found to be tubulin polymerization inhibitors. In contrast, one of the compounds was found to stabilize tubulin to the same extent as the anticancer drug docetaxel. Molecular modeling suggested that the tubulin inhibitors bind to the colchicine binding site of beta-tubulin while the novel tubulin stabilization agent seems to interact with the paclitaxel binding site.
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| 9. |
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| 10. |
- Fridén-Saxin, Maria, 1979, et al.
(author)
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Chroman-4-one and chromone based somatostatin beta-turn mimetics
- 2016
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In: European Journal of Medicinal Chemistry. - : Elsevier BV. - 0223-5234. ; 114, s. 59-64
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Journal article (peer-reviewed)abstract
- A scaffold approach has been used to develop somatostatin beta-turn mimetics based on chroman-4-one and chromone ring systems. Such derivatives could adopt conformations resembling type II or type II' beta-turns. Side chain equivalents of the crucial Trp8 and Lys9 in somatostatin were introduced in the 2- and 8-positions of the scaffolds using efficient reactions. Interestingly, this proof-of-concept study shows that 4 and 9 have K-i-values in the low mu M range when evaluated for their affinity for the sst2 and sst4 receptors. (C) 2016 Elsevier Masson SAS. All rights reserved.
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