ABSTRACT
Microwave assisted Diels-Alder cycloaddition of 5-Br-N-benzylpyridinone (2) with methyl acrylate is described to gain an easy access to 7-bromo-2-benzyl-3-oxo-2-aza-5 or 6-carbomethoxy bicyclo[2.2.2]oct-7-enes (3)-(6). The preparation of the ibogaine analogue 20-desethyl-(20-endo)-hydroxymethyl-11-demethoxyibogaine (17) is described by stereoselective hydrogenation of the C(7)-C(8) double bond. Biological evaluation showed an interesting in vitro binding profile toward dopamine transporter, serotonin transporter and opioid receptor systems accompanied by an antiwithdrawal effect in mice for hydroxymethyl 7-indolyl-2-aza-bicyclo[2.2.2]oct-2-ene (14). The simplification of the ibogaine structure appears as a promising approach toward the design of compounds that could reduce the withdrawal symptoms.
Subject(s)
Ibogaine/analogs & derivatives , Substance Withdrawal Syndrome/drug therapy , Animals , Ibogaine/chemical synthesis , Ibogaine/therapeutic use , Male , Mice , Molecular StructureABSTRACT
The methanol extract of Peucedanum zenkeri L. seeds showed antimicrobial activity which is concentrated in the n-hexane fraction. Bioactivity-guided chromatographic fractionation of the seeds of P. zenkeri led to the isolation and characterization of five major coumarins, umbelliprenin, imperatorin, bergapten, isopimpinellin and byakangelicin, as well as two minor coumarins, 7-methoxy coumarin and 5-hydroxy-8-methoxy psoralen. Amongst the isolated compounds only imperatorin, bergapten and isopimpinellin were found to possess anti-microbial activity.
Subject(s)
Anti-Infective Agents/pharmacology , Apiaceae/chemistry , Africa, Western , Anti-Bacterial Agents , Bacteria/drug effects , Coumarins/isolation & purification , Coumarins/pharmacology , Fungi/drug effects , Hexanes , Microbial Sensitivity Tests , Plants, Medicinal/chemistry , Seeds/chemistry , SolventsABSTRACT
Chromaproline and Chromaperidine, two recently synthesized and pharmacologically characterized nicotinic agonists, and Donepezil (Aricept), an acetylcholinesterase inhibitor approved for the treatment of memory loss, were evaluated for effects on performance of a visual recognition memory task (object recognition) and a spatial memory task (object placement). Ovariectomized female rats received the drugs chronically via subcutaneous Alzet minipumps. None of the drugs altered activity in the open field or the time spent exploring objects in the field. One week following initiation of treatment, all three drugs enhanced performance of the visual recognition task, but only Donepezil enhanced performance of the spatial memory task. With a longer period of treatment (3 weeks), the nicotinic agonist Chromaproline also enhanced object placement performance. Current results show the memory-enhancing efficacy of Donepezil in two additional memory tasks in rats and suggest that the novel nicotinic agonists, Chromaproline and Chromaperidine, may also be useful new drugs for the treatment of memory impairments/loss.
