Development of novel adenosine receptor ligands based on the 3-amidocoumarin scaffold

• Type: Article in International Scientific Journal
• Date: 2015

Authors

Maria J Matos (Author) Other; Santiago Vilar (Author) Other; Sonja Kachler (Author) Other; Maria Celeiro (Author) Other; Saleta Vazquez Rodriguez (Author) Other; Lourdes Santana (Author) Other; Eugenio Uriarte (Author) Other; George Hripcsak (Author) Other; Fernanda Borges (Author) FCUP; Karl Norbert Klotz (Author) Other

Journal

Title: Bioorganic Chemistry

Vol. 61

ISSN: 0045-2068

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 10 Citations

Scopus - 10 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

Other information

Authenticus ID: P-00G-B0K

Abstract (EN): With the aim of finding new adenosine receptor (AR) ligands presenting the 3-amidocoumarin scaffold, a study focusing on the discovery of new chemical entities was carried out. The synthesized compounds 1-8 were evaluated in radioligand binding (A(1), A(2A) and A(3)) and adenylyl cyclase activity (A(2B)) assays in order to determine their affinity for human AR subtypes. The 3-benzamide derivative 4 showed the highest affinity of the whole series and was more than 30-fold selective for the A(3) AR (K-i = 3.24 mu M). The current study supported that small structural changes in this scaffold allowed modulating the affinity resulting in novel promising classes of A(1), A(2A), and/or A(3) AR ligands. We also performed docking calculations in hA(2A) and hA(3) to identify the hypothetical binding mode for the most active compounds. In addition, some ADME properties were calculated in order to better understand the potential of these compounds as drug candidates. (C) 2015 Elsevier Inc. All rights reserved.

Language: English

Type (Professor's evaluation): Scientific