Tryptamine-derived alkaloids from Annonaceae exerting neurotrophin-like properties on primary dopaminergic neurons.
N-fatty acyl tryptamines constitute a scarce group of natural compounds mainly encountered in Annonaceous plants. No biological activity was reported so far for these rare molecules. This study investigated the neurotrophic properties of these natural tryptaminic derivatives on dopaminergic (DA) neurons in primary mesencephalic cultures. A structure-activity relationships study led us to precise the role of a nitrogen atom into the aliphatic chain conferring to the compounds a combined neuroprotective and neuritogenic activity in the nanomolar range. The potent antioxidant activity of these natural products seems to be involved in part of their mechanism of action. This study provides the first description of natural neurotrophin mimetics present in Annonaceae extracts, and led to the biological characterization of compounds, which present a potential interest in neurodegenerative diseases such as Parkinson's disease.
Schmidt
Fanny
F
Centre National de la Recherche Scientifique, Laboratoire de Pharmacognosie, UMR 8076 BioCIS, Faculté de Pharmacie, Université Paris-Sud 11, 5 rue J.B. Clément 92296 Châtenay-Malabry Cedex, France. fanny.schmidt@gmail.com
Le Douaron
Gael
G
Champy
Pierre
P
Amar
Majid
M
Séon-Méniel
Blandine
B
Raisman-Vozari
Rita
R
Figadère
Bruno
B
D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D029061:Annonaceae / Q000737:chemistry*; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000378:metabolism; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism; D005260:Female; D008297:Male; D008636:Mesencephalon / Q000166:cytology; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014363:Tryptamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*
D000470:Alkaloids; D000975:Antioxidants; D018696:Neuroprotective Agents; D014363:Tryptamines; C030820:tryptamine; D004298:Dopamine