The α7 nicotinic acetylcholine receptor (α7 nAChR) is widely distributed in the human organism, where it mediates many physiological and pathological processes. In the central nervous system, it is expressed both on neuronal and non-neuronal cells, where it controls cognitive and mnemonic processes, sensory gating and neuroinflammation, and it is thus involved in the etiopathology of several diseases, such as Alzheimer’s, depression, schizophrenia, and attention-deficit/hyperactivity disorder (ADHD). In the periphery, it is essential for the survival of α7 dependent tumours, which are the most predominant type of lung cancer in the population. Therefore, α7 modulators have a huge therapeutic potential, but their clinical translation is hampered by the lack of adequate safety, generally because of off-target effects. In addition, even though a vast pharmacological toolset to study α7 mediated functions has been developed, control of central α7 nAChRs with high spatiotemporal precision is missing. To address these issues, we have developed a small group of photoswitchable α7 nAChR ligands. Light is in fact an unparalleled tool as a noninvasive regulatory signal for pharmacological and biological applications, since it can be delivered with high spatiotemporal precision. An emerging light-based approach is photopharmacology, which relies on the use of reversibly photoswitching drugs (Figure 1). Our photoisomerizable compounds were designed by “azologization” of selective α7 nAChR agonists. In this work, I will present the design, the chemical synthesis, and the photochromic characterization of these novel putative photoswitchable α7 ligands.

Photoswitchable ligands for light-mediated control of α7 nicotinic acetylcholine receptors: design, synthesis and photochromic characterization / C. Papotto, R. Sortino, H. Lee, B. Preda, C. Matera, M. De Amici, P. Gorostiza, C. Dallanoce - In: 13th Young Medicinal Chemist Symposium : nuove prospettive in clinica farmaceutica[s.l] : Società Chimica Italiana, 2021. - pp. 117-117 (( Intervento presentato al 13. convegno Young Medicinal Chemist Symposium : Nuove Prospettive in Chimica Farmaceutica tenutosi a Virtual Symposium nel 2021.

Photoswitchable ligands for light-mediated control of α7 nicotinic acetylcholine receptors: design, synthesis and photochromic characterization

C. Papotto
Primo
;
C. Matera;M. De Amici;C. Dallanoce
Ultimo
2021

Abstract

The α7 nicotinic acetylcholine receptor (α7 nAChR) is widely distributed in the human organism, where it mediates many physiological and pathological processes. In the central nervous system, it is expressed both on neuronal and non-neuronal cells, where it controls cognitive and mnemonic processes, sensory gating and neuroinflammation, and it is thus involved in the etiopathology of several diseases, such as Alzheimer’s, depression, schizophrenia, and attention-deficit/hyperactivity disorder (ADHD). In the periphery, it is essential for the survival of α7 dependent tumours, which are the most predominant type of lung cancer in the population. Therefore, α7 modulators have a huge therapeutic potential, but their clinical translation is hampered by the lack of adequate safety, generally because of off-target effects. In addition, even though a vast pharmacological toolset to study α7 mediated functions has been developed, control of central α7 nAChRs with high spatiotemporal precision is missing. To address these issues, we have developed a small group of photoswitchable α7 nAChR ligands. Light is in fact an unparalleled tool as a noninvasive regulatory signal for pharmacological and biological applications, since it can be delivered with high spatiotemporal precision. An emerging light-based approach is photopharmacology, which relies on the use of reversibly photoswitching drugs (Figure 1). Our photoisomerizable compounds were designed by “azologization” of selective α7 nAChR agonists. In this work, I will present the design, the chemical synthesis, and the photochromic characterization of these novel putative photoswitchable α7 ligands.
Settore CHIM/08 - Chimica Farmaceutica
Settore BIO/14 - Farmacologia
Società Chimica Italiana
Book Part (author)
File in questo prodotto:
File Dimensione Formato  
book of abstracts_final_compressed.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 4.03 MB
Formato Adobe PDF
4.03 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Abstract.pdf

accesso riservato

Tipologia: Post-print, accepted manuscript ecc. (versione accettata dall'editore)
Dimensione 214.89 kB
Formato Adobe PDF
214.89 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/856062
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact