Your browser doesn't support javascript.
loading
Design, synthesis and evaluation of pentacycloundecane and hexacycloundecane propargylamine derivatives as multifunctional neuroprotective agents.
Zindo, Frank T; Malan, Sarel F; Omoruyi, Sylvester I; Enogieru, Adaze B; Ekpo, Okobi E; Joubert, Jacques.
Afiliación
  • Zindo FT; Pharmaceutical Chemistry, School of Pharmacy, University of the Western Cape, Private Bag X17, Bellville, 7535, South Africa.
  • Malan SF; Pharmaceutical Chemistry, School of Pharmacy, University of the Western Cape, Private Bag X17, Bellville, 7535, South Africa.
  • Omoruyi SI; Department of Medical Biosciences, University of the Western Cape, Private Bag X17, Cape Town, Bellville, 7535, South Africa.
  • Enogieru AB; Department of Medical Biosciences, University of the Western Cape, Private Bag X17, Cape Town, Bellville, 7535, South Africa.
  • Ekpo OE; Department of Medical Biosciences, University of the Western Cape, Private Bag X17, Cape Town, Bellville, 7535, South Africa.
  • Joubert J; Pharmaceutical Chemistry, School of Pharmacy, University of the Western Cape, Private Bag X17, Bellville, 7535, South Africa. Electronic address: jjoubert@uwc.ac.za.
Eur J Med Chem ; 163: 83-94, 2019 Feb 01.
Article en En | MEDLINE | ID: mdl-30503945
The multifactorial pathophysiology of neurodegenerative disorders remains one of the main challenges in the design of a single molecule that may ultimately prevent the progression of these disorders in affected patients. In this article, we report on twelve novel polycyclic amine cage derivatives, synthesized with or without a propargylamine function, designed to possess inherent multifunctional neuroprotective activity. The MTT cytotoxicity assay results showed the SH-SY5Y human neuroblastoma cells to be viable with the twelve compounds, particularly at concentrations less than 10 µM. The compounds also showed significant neuroprotective activity, ranging from 31% to 61% at 1 µM, when assayed on SH-SY5Y human neuroblastoma cells in which neurodegeneration was induced by MPP+. Calcium regulation assays conducted on the same cell line showed the compounds to be significant VGCC blockers with activity ranging from 26.6% to 51.3% at 10 µM; as well as significant NMDAr antagonists with compound 5 showing the best activity of 88.3% at 10 µM. When assayed on human MAO isoenzymes, most of the compounds showed significant inhibitory activity, with compound 5 showing the best activity (MAO-B: IC50 = 1.70 µM). Generally, the compounds were about 3-52 times more selective to the MAO-B isoenzyme than the MAO-A isoenzyme. Based on the time-dependency studies conducted, the compounds can be defined as reversible MAO inhibitors. Several structure activity relationships were derived from the various assays conducted, and the compounds' possible putative binding modes within the MAO-B enzyme cavity were assessed in silico.
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: Pargilina / Propilaminas / Fármacos Neuroprotectores Límite: Humans Idioma: En Revista: Eur J Med Chem Año: 2019 Tipo del documento: Article País de afiliación: Sudáfrica Pais de publicación: Francia
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: Pargilina / Propilaminas / Fármacos Neuroprotectores Límite: Humans Idioma: En Revista: Eur J Med Chem Año: 2019 Tipo del documento: Article País de afiliación: Sudáfrica Pais de publicación: Francia