Novel positive allosteric modulators of A2B adenosine receptor acting as bone mineralisation promoters. (1st January 2021)

• Record Type: Journal Article
• Authors: Barresi, Elisabetta; Giacomelli, Chiara; Marchetti, Laura; Baglini, Emma; Salerno, Silvia; Greco, Giovanni; Da Settimo, Federico; Martini, Claudia; Trincavelli, Maria Letizia; Taliani, Sabrina
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 36:Number 1(2021)
• Page Start: 287
• Page End: 295
• Publication Date: 2021-01-01
• Subjects: A2B adenosine receptor -- allosteric modulators -- mesenchymal stem cell -- bone formation -- BAY60-6583; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2020.1862103
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: Small-molecules acting as positive allosteric modulators (PAMs) of the A2B adenosine receptor (A2B AR) could potentially represent a novel therapeutic strategy for pathological conditions characterised by altered bone homeostasis, including osteoporosis. We investigated a library of compounds (4 -13 ) exhibiting different degrees of chemical similarity with three indole derivatives (1 -3 ), which have been recently identified by us as PAMs of the A2B AR able to promote mesenchymal stem cell differentiation and bone formation. Evaluation of mineralisation activity of 4 -13 in the presence and in the absence of the agonist BAY60-6583 allowed the identification of lead compounds with therapeutic potential as anti-osteoporosis agents. Further biological characterisation of one of the most performing compounds, the benzofurane derivative 9, confirmed that such a molecule behaves as PAM of the A2B AR.