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.

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

Barresi E.
Co-primo
;
Giacomelli C.
Co-primo
;
Marchetti L.;Salerno S.;Da Settimo F.;Martini C.;Trincavelli M. L.
Penultimo
;
Taliani S.
Ultimo
2021-01-01

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.
2021
Barresi, E.; Giacomelli, C.; Marchetti, L.; Baglini, E.; Salerno, S.; Greco, G.; Da Settimo, F.; Martini, C.; Trincavelli, M. L.; Taliani, S.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/1077442
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