ynthesis and dopamine receptor binding of dihydrexidine and SKF 38393 catecholamine-based analogue

Autor(es):Mostrar menos -

da Silva, Suzane Rosa ^[1] ; Kalaba, Predrag ^[2] ; Fabisikova, Anna ^[3] ; Zehl, Martin ^{[4, 3]} ; Dragatevie, Vladimir ^[2] ; dos Anjos, Luana Ribeiro ^[1] ; Neill, Philip John ^[2] ; Wieder, Marcus ^[2] ; Prado-Roller, Alexander ^[5] ; Gajic, Natalie ^[5] ; Palaretti, Vinicius ^[6] ; Jose da Silva, Gil Valdo ^[6] ; Pifl, Christian ^[7] ; Lubec, Gert ^[8] ; Perez Gonzalez, Eduardo R. ^[1]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ, Fac Sci & Technol, Dept Chem & Biochem, Lab Fine Organ Chem, BR-19060900 Presidente Prudente, SP - Brazil

^[2] Univ Vienna, Fac Life Sci, Dept Pharmaceut Chem, Althanstr 14, A-1090 Vienna - Austria

^[3] Univ Vienna, Fac Chem, Mass Spectrometry Ctr, Wahringer Str 38, A-1090 Vienna - Austria

^[4] Univ Vienna, Fac Chem, Dept Analyt Chem, Wahringer Str 38, A-1090 Vienna - Austria

^[5] Univ Vienna, Ctr Xray Struct Anal, Fac Chem, Wahringer Str 40-42, A-1090 Vienna - Austria

^[6] Univ Sao Paulo, Fac Philosophy Sci & Letters Ribeirao Preto, Dept Chem, Ave Bandeirantes 3900, BR-14040901 Ribeirao Preto, SP - Brazil

^[7] Med Univ Vienna, Ctr Brain Res, Dept Mol Neurosci, Spitalgasse 4, A-1090 Vienna - Austria

^[8] Paracelsus Med Univ, Dept Neuroprote, A-5020 Salzburg - Austria

• Tipo de documento: Artigo Científico
• Fonte: Amino Acids; v. 54, n. 1 NOV 2021.
• Citações Web of Science: 0

Resumo

Dopamine is an important neurotransmitter that regulates numerous essential functions, including cognition and voluntary movement. As such, it serves as an important scaffold for synthesis of novel analogues as part of drug development effort to obtain drugs for treatment of neurodegenerative diseases, such as Parkinson's disease. To that end, similarity search of the ZINC database based on two known dopamine-1 receptor (D1R) agonists, dihydrexidine (DHX) and SKF 38393, respectively, was used to predict novel chemical entities with potential binding to D1R. Three compounds that showed the highest similarity index were selected for synthesis and bioactivity profiling. All main synthesis products as well as the isolated intermediates, were properly characterized. The physico-chemical analyses were performed using HRESIMS, GC/MS, LC/MS with UV-Vis detection, and FTIR, H-1 NMR and C-13 NMR spectroscopy. Binding to D1 and D2 receptors and inhibition of dopamine reuptake via dopamine transporter were measured for the synthesized analogues of DHX and SKF 38393. (AU)

• Processo FAPESP: 16/10149-0 - Síntese e caracterização química e biológica de análogos de 2-fenilquinazolinas-4-substituídas como novos inibidores atípicos do transporte e recaptação da dopamina (DAT)
• Beneficiário: Eduardo Rene Perez Gonzalez
• Modalidade de apoio: Bolsas no Exterior - Pesquisa
• Processo FAPESP: 18/00581-7 - Síntese e caraterização de compostos orgânicos com potencial como novos fármacos para disfunções de canais iônicos, tratamento da leishmânia e antitumorais.
• Beneficiário: Eduardo Rene Perez Gonzalez
• Modalidade de apoio: Auxílio à Pesquisa - Regular