Your browser doesn't support javascript.
loading
Design, synthesis, and evaluation of 3,7-substituted coumarin derivatives as multifunctional Alzheimer's disease agents.
Mzezewa, Sheunopa C; Omoruyi, Sylvester I; Zondagh, Luke S; Malan, Sarel F; Ekpo, Okobi E; Joubert, Jacques.
Afiliación
  • Mzezewa SC; Department of Pharmaceutical Chemistry, School of Pharmacy, University of the Western Cape, Bellville, South Africa.
  • Omoruyi SI; Department of Medical Biosciences, University of the Western Cape, Bellville, South Africa.
  • Zondagh LS; Department of Pharmaceutical Chemistry, School of Pharmacy, University of the Western Cape, Bellville, South Africa.
  • Malan SF; Department of Pharmaceutical Chemistry, School of Pharmacy, University of the Western Cape, Bellville, South Africa.
  • Ekpo OE; Department of Medical Biosciences, University of the Western Cape, Bellville, South Africa.
  • Joubert J; Department of Pharmaceutical Chemistry, School of Pharmacy, University of the Western Cape, Bellville, South Africa.
J Enzyme Inhib Med Chem ; 36(1): 1607-1621, 2021 Dec.
Article en En | MEDLINE | ID: mdl-34281458
Multitarget directed ligands (MTDLs) are emerging as promising treatment options for Alzheimer's disease (AD). Coumarin derivatives serve as a good starting point for designing MTDLs due to their inherent inhibition of monoamine oxidase (MAO) and cholinesterase enzymes, which are complicit in AD's complex pathophysiology. A preliminary series of 3,7-substituted coumarin derivatives were synthesised and evaluated for enzyme inhibitory activity, cytotoxicity as well as neuroprotective ability. The results indicated that the compounds are weak cholinesterase inhibitors with five compounds demonstrating relatively potent inhibition and selectivity towards MAO-B with IC50 values between 0.014 and 0.498 hx00B5;µM. Significant neuroprotective effects towards MPP+-compromised SH-SY5Y neuroblastoma cells were also observed, with no inherent cytotoxicity at 10 µM for all compounds. The overall results demonstrated that substitution of the phenylethyloxy moiety at the 7-position imparted superior general activity to the derivatives, with the propargylamine substitution at the 3-position, in particular, displaying the best MAO-B selectivity and neuroprotection.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diseño de Fármacos / Fármacos Neuroprotectores / Cumarinas / Enfermedad de Alzheimer / Inhibidores de la Monoaminooxidasa Límite: Humans Idioma: En Revista: J Enzyme Inhib Med Chem Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2021 Tipo del documento: Article País de afiliación: Sudáfrica Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diseño de Fármacos / Fármacos Neuroprotectores / Cumarinas / Enfermedad de Alzheimer / Inhibidores de la Monoaminooxidasa Límite: Humans Idioma: En Revista: J Enzyme Inhib Med Chem Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2021 Tipo del documento: Article País de afiliación: Sudáfrica Pais de publicación: Reino Unido