Novel positive allosteric modulators of A2B adenosine receptor acting as bone mineralisation promoters

• Main Authors: Elisabetta Barresi, Chiara Giacomelli, Laura Marchetti, Emma Baglini, Silvia Salerno, Giovanni Greco, Federico Da Settimo, Claudia Martini, Maria Letizia Trincavelli, Sabrina Taliani
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2021-01-01
• Series: Journal of Enzyme Inhibition and Medicinal Chemistry
• Subjects: a2b adenosine receptor; allosteric modulators; mesenchymal stem cell; bone formation; bay60-6583
• Online Access: http://dx.doi.org/10.1080/14756366.2020.1862103

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.