RT Journal Article
T1 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
A1 Abatematteo, Francesca Serena
A1 Majellaro, Maria
A1 Montsch, Bianca
A1 Prieto Díaz, Rubén
A1 Niso, Mauro
A1 Contino, Marialessandra
A1 Stefanachi, Angela
A1 Riganti, Chiara
A1 Mangiatordi, Giuseppe Felice
A1 Delre, Pietro
A1 Heffeter, Petra
A1 Sotelo Pérez, Eddy
A1 Abate, Carmen
K1 Assays
K1 Fluorescence
K1 Indoles
K1 Ligands
K1 Receptors
AB 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
PB ACS Publications
SN 0022-2623
YR 2023
FD 2023
LK http://hdl.handle.net/10347/32286
UL http://hdl.handle.net/10347/32286
LA eng
NO Abatematteo, F.S., Majellaro, M., Montsch, B., Prieto Díaz, R., Niso, M., Contino, M., Stefanachi, A., Riganti, C., Mangiatordi, G.F., Delre, P., Heffeter, P., Sotelo, E., Abate, C. (2023). 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. "Journal of Medicinal Chemistry", vol.66, 3798-3817
NO This work was financially supported by the Consellería deCultura, Educación e Ordenación Universitaria of the GalicianGovernment (Grant ED431B 2020/43), Centro Singular deInvestigación de Galicia accreditation 2019-2022 (ED431G2019/03), and the European Regional Development Fund(ERDF). B.M. was financed by the Austrian Science Fund(Grant P31923). F.S.A. was partially funded by STRATAGEMCOST Action 17104. The authors thank Prof. Matilde Colellafrom the Università degli Studi di Bari for the interestingdiscussion on confocal microscopy.
DS Minerva
RD 29 abr 2026