Identification and synthesis of novel alkaloids from the root system of Nicotiana tabacum: affinity for neuronal nicotinic acetylcholine receptors.
A novel pyridine derivative, 3,5-bis-(1-methyl-pyrrolidin-2-yl)-pyridine, and a pair of diastereomers of 1,1'-dimethyl-[2,3']bipyrrolidinyl were isolated from the root of Nicotiana tabacum plants and identified as novel alkaloids by GC-MS analysis. The structures of these new alkaloids were confirmed by total synthesis. The affinities of these novel alkaloids, and other structurally related compounds for alpha4beta2*, alpha7* neuronal nicotinic acetylcholine receptors (nAChRs), and for nAChRs mediating nicotine-evoked dopamine release from rat striatum were also assessed. The results indicate that these compounds do not interact with alpha7* nAChRs, but inhibit [3H]nicotine binding to the alpha4beta2* nAChR subtype. The results also demonstrate that these compounds act as antagonists at nAChRs mediating nicotine-evoked dopamine release from rat striatum.
Wei
Xiaochen
X
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA.
Sumithran
Sangeetha P
SP
Deaciuc
A Gabriela
AG
Burton
Harold R
HR
Bush
Lowell P
LP
Dwoskin
Linda P
LP
Crooks
Peter A
PA
D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D009538:Nicotine / Q000378:metabolism; D018517:Plant Roots / Q000737:chemistry; D011978:Receptors, Nicotinic / Q000187:drug effects*; D014026:Nicotiana / Q000737:chemistry*
D000470:Alkaloids; D011978:Receptors, Nicotinic; D009538:Nicotine; D004298:Dopamine