Unknown

Dataset Information

0

Development of Fluorescent 4-[4-(3H-Spiro[isobenzofuran-1,4'-piperidin]-1'-yl)butyl]indolyl Derivatives as High-Affinity Probes to Enable the Study of σ Receptors via Fluorescence-Based Techniques.

ABSTRACT: Sigma (σ) receptor subtypes, σ1 and σ2, are targets of wide pharmaceutical interest. The σ2 receptor holds promise for the development of diagnostics and therapeutics against cancer and Alzheimer's disease. Nevertheless, little is known about the mechanisms activated by the σ2 receptor. To contribute to the exploitation of its therapeutic potential, we developed novel specific fluorescent ligands. Indole derivatives bearing the N-butyl-3H-spiro[isobenzofuran-1,4'-piperidine] portion were functionalized with fluorescent tags. Nanomolar-affinity fluorescent σ ligands, spanning from green to red to near-infrared emission, were obtained. Compounds 19 (σ pan affinity) and 29 (σ2 selective), which displayed the best compromise between pharmacodynamic and photophysical properties, were investigated in flow cytometry, confocal, and live cell microscopy, demonstrating their specificity for the σ2 receptor. To the best of our knowledge, these are the first red-emitting fluorescent σ2 ligands, validated as powerful tools for the study of σ2 receptors via fluorescence-based techniques.

SUBMITTER: Abatematteo FS 

PROVIDER: S-EPMC10041534 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Development of Fluorescent 4-[4-(3<i>H</i>-Spiro[isobenzofuran-1,4'-piperidin]-1'-yl)butyl]indolyl Derivatives as High-Affinity Probes to Enable the Study of σ Receptors via Fluorescence-Based Techniques.

Abatematteo Francesca Serena FS   Majellaro Maria M   Montsch Bianca B   Prieto-Díaz Rubén R   Niso Mauro M   Contino Marialessandra M   Stefanachi Angela A   Riganti Chiara C   Mangiatordi Giuseppe Felice GF   Delre Pietro P   Heffeter Petra P   Sotelo Eddy E   Abate Carmen C  

Journal of medicinal chemistry 20230315 6

Sigma (σ) receptor subtypes, σ<sub>1</sub> and σ<sub>2</sub>, are targets of wide pharmaceutical interest. The σ<sub>2</sub> receptor holds promise for the development of diagnostics and therapeutics against cancer and Alzheimer's disease. Nevertheless, little is known about the mechanisms activated by the σ<sub>2</sub> receptor. To contribute to the exploitation of its therapeutic potential, we developed novel specific fluorescent ligands. Indole derivatives bearing the <i>N-</i>butyl-3<i>H</i>  ...[more]

Similar Datasets

Unknown 1,4-Bis(piperidin-1-ylcarbon-yl)benzene.
| S-EPMC2914991 | biostudies-literature
Unknown One-Pot Synthesis of Spiro-isobenzofuran Compounds <i>via</i> the Sequential Condensation/Oxidation Reaction of Ninhydrin with 4-Amino-1,2-naphthoquinones/2-Amino-1,4-naphthoquinones under Mild Conditions.
| S-EPMC7392522 | biostudies-literature
Unknown PIFA-mediated selenylative spirocyclization of indolyl ynones: facile access to selenated spiro[cyclopentenone-1,3'-indoles].
| S-EPMC9549584 | biostudies-literature
Unknown 1,4-Bis(benz-yloxy)-2-tert-butyl-benzene.
| S-EPMC2960852 | biostudies-other
Unknown (2R,3R)-1,4-Dioxa-spiro-[4.4]nonane-2,3-di-carb-oxy-lic and (2R,3R)-1,4-dioxa-spiro-[4.5]decane-2,3-di-carb-oxy-lic acids.
| S-EPMC6073000 | biostudies-literature
Unknown 3-Butyl-2-phenyl-1,3-thia-zolidine-1,4-dione.
| S-EPMC2979582 | biostudies-literature
Unknown tert-Butyl 6-oxo-2,7-diaza-spiro[4.4]nonane-2-carboxyl-ate.
| S-EPMC3239116 | biostudies-literature
Unknown Bis(1,2,2,6,6-penta-methyl-piperidin-4-yl) 2-butyl-2-(3,5-di-tert-butyl-4-hydroxy-benz-yl)malonate (Tinuvin 144).
| S-EPMC2970408 | biostudies-literature
Unknown Synthesis of spiro-2,6-dioxopiperazine and spiro-2,6-dioxopyrazine scaffolds using amino acids in a three-component reaction to generate potential Sigma-1 (σ<sub>1</sub>) receptor selective ligands.
| S-EPMC6361672 | biostudies-literature
Unknown Di-tert-butyl cyclo-hex-2-ene-1,4-diyl dicarbonate.
| S-EPMC2971395 | biostudies-literature