| Texto completo | |
| Autor(es): |
Correa, Michelle F.
;
Reiner, David
;
Fernandes, Gustavo A. B.
;
Varela, Marina T.
;
Aranha, Cecilia M. S. Q.
;
Stark, Holger
;
Fernandes, Joao Paulo S.
Número total de Autores: 7
|
| Tipo de documento: | Artigo Científico |
| Fonte: | JOURNAL OF CHEMICAL SCIENCES; v. 132, n. 1, p. 6-pg., 2019-12-01. |
| Resumo | |
Histamine and dopamine neuronal pathways display interesting overlapping in the CNS, especially in the limbic areas, making them very attractive to designing drugs with synergistic and/or additive effects. The roles of these systems to treat schizophrenia, drug addiction, Parkinson's and Alzheimer's diseases, among others are widely known. The LINS01 compounds were previously reported as histamine H-3 receptor (H3R) antagonists and some of them are under evaluation in rodent memory models. Considering their pharmacological potential and similarities to literature dopamine D-2 receptor (D2R) and dopamine D-3 receptor (D3R) ligands, this work aimed to evaluate these compounds as ligands these receptors by using [H-3]spiperone displacement assays. A set of 11 compounds containing the dihydrobenzofuranyl-piperazine core with substituents at 5-position of dihydrobenzofuran ring and at the piperazine nitrogen was examined. The compounds showed low to moderate affinities at both, D2R and D3R. N-Phenyl compounds LINS01005 (1d), LINS01011 (1h), LINS01012 (1i) and LINS01016 (1k) showed the highest affinities in the set to D3R (K-i 0.3-1.5 mu M), indicating that N-phenylpiperazine moiety increases the affinity to this receptor subtype with some selectivity, since they showed lower affinities to D2R (K-i 1.3-5.5 mu M). With the LINS01 compounds showing moderate binding affinity, new lead structures for optimization with regards to combined H3R and D2R/D3R-ligands are provided. (AU) | |
| Processo FAPESP: | 18/03918-2 - Avaliação da atividade antiparasitária e da citotoxicidade de derivados de produtos naturais em Trypanosoma cruzi: planejamento e síntese de análogos potencialmente superiores |
| Beneficiário: | Marina Themoteo Varela |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado |
| Processo FAPESP: | 16/25028-3 - Anti-histamínicos H3R/H4R como agentes pró-cognitivos: uma abordagem multialvo |
| Beneficiário: | João Paulo dos Santos Fernandes |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 18/04488-1 - Ligantes histaminérgicos e dopaminérgicos como agentes pró-cognitivos: Síntese e avaliação de ariloxialquilpiperazinas |
| Beneficiário: | Cecília Maria Simões de Queiroz Aranha |
| Modalidade de apoio: | Bolsas no Brasil - Iniciação Científica |
| Processo FAPESP: | 17/05441-6 - Diidrobenzofuranil-fenilpiperazinas como agentes vasodilatadores: síntese e avaliação de análogos do lins01005 |
| Beneficiário: | Gustavo Ariel Borges Fernandes |
| Modalidade de apoio: | Bolsas no Brasil - Iniciação Científica |