PMID- 32961824
OWN - NLM
STAT- MEDLINE
DCOM- 20210310
LR  - 20210310
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 25
IP  - 18
DP  - 2020 Sep 19
TI  - Adenosine Receptor Ligands: Coumarin-Chalcone Hybrids as Modulating Agents on the 
      Activity of hARs.
LID - 10.3390/molecules25184306 [doi]
LID - 4306
AB  - Adenosine receptors (ARs) play an important role in neurological and psychiatric 
      disorders such as Alzheimer's disease, Parkinson's disease, epilepsy and 
      schizophrenia. The different subtypes of ARs and the knowledge on their densities 
      and status are important for understanding the mechanisms underlying the 
      pathogenesis of diseases and for developing new therapeutics. Looking for new 
      scaffolds for selective AR ligands, coumarin-chalcone hybrids were synthesized 
      (compounds 1-8) and screened in radioligand binding (hA(1), hA(2A) and hA(3)) and 
      adenylyl cyclase (hA(2B)) assays in order to evaluate their affinity for the four 
      human AR subtypes (hARs). Coumarin-chalcone hybrid has been established as a new 
      scaffold suitable for the development of potent and selective ligands for hA(1) 
      or hA(3) subtypes. In general, hydroxy-substituted hybrids showed some affinity 
      for the hA(1), while the methoxy counterparts were selective for the hA(3). The 
      most potent hA(1) ligand was compound 7 (K(i) = 17.7 microM), whereas compound 4 was 
      the most potent ligand for hA(3) (K(i) = 2.49 microM). In addition, docking studies 
      with hA(1) and hA(3) homology models were established to analyze the 
      structure-function relationships. Results showed that the different residues 
      located on the protein binding pocket could play an important role in ligand 
      selectivity.
FAU - Vazquez-Rodriguez, Saleta
AU  - Vazquez-Rodriguez S
AD  - Departamento de Quimica Organica, Facultad de Farmacia, Universidad de Santiago 
      de Compostela, 15782 Santiago de Compostela, Spain.
FAU - Vilar, Santiago
AU  - Vilar S
AD  - Departamento de Quimica Organica, Facultad de Farmacia, Universidad de Santiago 
      de Compostela, 15782 Santiago de Compostela, Spain.
FAU - Kachler, Sonja
AU  - Kachler S
AD  - Institut fur Pharmakologie und Toxikologie, Universitat Wurzburg, 97078 Wurzburg, 
      Germany.
FAU - Klotz, Karl-Norbert
AU  - Klotz KN
AD  - Institut fur Pharmakologie und Toxikologie, Universitat Wurzburg, 97078 Wurzburg, 
      Germany.
FAU - Uriarte, Eugenio
AU  - Uriarte E
AD  - Departamento de Quimica Organica, Facultad de Farmacia, Universidad de Santiago 
      de Compostela, 15782 Santiago de Compostela, Spain.
AD  - Instituto de Ciencias Quimicas Aplicadas, Universidad Autonoma de Chile, 7500912 
      Santiago, Chile.
FAU - Borges, Fernanda
AU  - Borges F
AD  - CIQUP/Department of Chemistry and Biochemistry, Faculty of Sciences, University 
      of Porto, Rua Campo Alegre 687, 4169-007 Porto, Portugal.
FAU - Matos, Maria Joao
AU  - Matos MJ
AD  - Departamento de Quimica Organica, Facultad de Farmacia, Universidad de Santiago 
      de Compostela, 15782 Santiago de Compostela, Spain.
AD  - CIQUP/Department of Chemistry and Biochemistry, Faculty of Sciences, University 
      of Porto, Rua Campo Alegre 687, 4169-007 Porto, Portugal.
LA  - eng
GR  - ED481B 2014/027-0, ED481B 2014/086-0 and ED481B 2018/007/Xunta de Galicia/
GR  - CEECIND/02423/2018/Fundacao para a Ciencia e Tecnologia/
PT  - Journal Article
DEP - 20200919
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - 0 (Chalcones)
RN  - 0 (Ligands)
RN  - 0 (Receptor, Adenosine A1)
RN  - 0 (Receptor, Adenosine A2A)
RN  - 0 (Receptor, Adenosine A3)
RN  - 5S5A2Q39HX (Chalcone)
SB  - IM
MH  - Binding Sites
MH  - Chalcone/*chemistry/metabolism
MH  - Chalcones/*chemistry/metabolism
MH  - Drug Design
MH  - Humans
MH  - Kinetics
MH  - Ligands
MH  - Molecular Docking Simulation
MH  - Protein Binding
MH  - Receptor, Adenosine A1/chemistry/*metabolism
MH  - Receptor, Adenosine A2A/chemistry/*metabolism
MH  - Receptor, Adenosine A3/chemistry/*metabolism
MH  - Structure-Activity Relationship
PMC - PMC7571217
OTO - NOTNLM
OT  - adenosine receptors
OT  - binding affinity
OT  - chalcone
OT  - coumarin
OT  - docking
OT  - neurodegenerative diseases
COIS- The authors declare no conflict of interest.
EDAT- 2020/09/24 06:00
MHDA- 2021/03/11 06:00
PMCR- 2020/09/19
CRDT- 2020/09/23 01:02
PHST- 2020/08/27 00:00 [received]
PHST- 2020/09/15 00:00 [revised]
PHST- 2020/09/18 00:00 [accepted]
PHST- 2020/09/23 01:02 [entrez]
PHST- 2020/09/24 06:00 [pubmed]
PHST- 2021/03/11 06:00 [medline]
PHST- 2020/09/19 00:00 [pmc-release]
AID - molecules25184306 [pii]
AID - molecules-25-04306 [pii]
AID - 10.3390/molecules25184306 [doi]
PST - epublish
SO  - Molecules. 2020 Sep 19;25(18):4306. doi: 10.3390/molecules25184306.