The Skeletal Structure of Lobinaline<sup>1</sup>

Robison, Michael M.; Pierson, William G.; Dorfman, Leon M.; Lambert, Bernard; Lucas, Robert A.

doi:10.1021/jo01348a027

Cited by 15 publications

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“…These results indicated the presence of a putatively novel multifunctional plant metabolite. GC-MS analysis of the CHCl 3 sub-fraction revealed lobinaline, the major alkaloid present in L. cardinalis , as the most abundant constituent (AUC = 70.15%) of the sub-fraction [50, 76–79]. The identity of lobinaline, a complex binitrogenous alkaloid, was confirmed based on previously reported structural and MS data [50, 76, 78].…”

Section: Resultssupporting

confidence: 68%

“…In the present study, the multifunctional alkaloid lobinaline was identified as the major bioactive metabolite present in L. cardinalis [50, 76–79]. The alkaloid possesses a unique polypharmacological profile functioning as a nicAchR agonist, DAT inhibitor, and free radical scavenger.…”

Section: Discussionmentioning

confidence: 99%

“…These configurations may be important for one or more of the pharmacological actions that we have reported. Robison et al[76] achieved a total synthesis of the ring structure but this was in the (easy) all trans configuration. Whether this possesses the same configuration and pharmacology as the molecule from the plant is unknown, but this is a direction for future studies.…”

Section: Discussionmentioning

confidence: 99%

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Novel multifunctional pharmacology of lobinaline, the major alkaloid from Lobelia cardinalis

et al. 2016

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In screening a library of plant extracts from ~1000 species native to the Southeastern United States, Lobelia cardinalis was identified as containing nicotinic acetylcholine receptor (nicAchR) binding activity which was relatively non-selective for the α4β2- and α7-nicAchR subtypes. This nicAchR binding profile is atypical for plant-derived nicAchR ligands, the majority of which are highly selective for α4β2-nicAchRs. Its potential therapeutic relevance is noteworthy since agonism of α4β2- and α7-nicAchRs is associated with anti-inflammatory and neuroprotective properties. Bioassay-guided fractionation of L. cardinalis extracts led to the identification of lobinaline, a complex binitrogenous alkaloid, as the main source of the unique nicAchR binding profile. Purified lobinaline was a potent free radical scavenger, displayed similar binding affinity at α4β2- and α7-nicAchRs, exhibited agonist activity at nicAchRs in SH-SY5Y cells, and inhibited [3H]-dopamine (DA) uptake in rat striatal synaptosomes. Lobinaline significantly increased fractional [3H] release from superfused rat striatal slices preloaded with [3H]-DA, an effect that was inhibited by the non-selective nicAchR antagonist mecamylamine. In vivo electrochemical studies in urethane-anesthetized rats demonstrated that lobinaline locally applied in the striatum significantly prolonged clearance of exogenous DA by the dopamine transporter (DAT). In contrast, lobeline, the most thoroughly investigated Lobelia alkaloid, is an α4β2-nicAchR antagonist, a poor free radical scavenger, and is a less potent DAT inhibitor. These previously unreported multifunctional effects of lobi-naline make it of interest as a lead to develop therapeutics for neuropathological disorders that involve free radical generation, cholinergic, and dopaminergic neurotransmission. These include neurodegenerative conditions, such as Parkinson’s disease, and drug abuse.

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Section: Resultssupporting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Novel multifunctional pharmacology of lobinaline, the major alkaloid from Lobelia cardinalis

et al. 2016

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“…The alkaloids in question for this application of the microfluidic device are those found in the cardinal flower, Lobelia cardinalis . L. cardinalis produces a binitrogenous alkaloid, lobinaline (decahydro‐1‐methyl‐5,7‐diphenyl‐6‐(3,4,5,6‐tetrahydro‐2‐pyridinyl)‐quinoline‐C 27 H 34 N 2 – Supporting Information ), recently shown to have inhibitory activity on the dopamine transporter (DAT) . In order to find novel metabolites with similar activity, Naprogenix (Lexington, KY) successfully transformed L. cardinalis to produce hairy root cultures expressing the human dopamine transporter (hDAT).…”

Section: Introductionmentioning

confidence: 99%

Microfluidic capillary zone electrophoresis mass spectrometry analysis of alkaloids in Lobelia cardinalis transgenic and mutant plant cell cultures

et al. 2019

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Application of a microfluidic CE* device for CZE‐MS allows for fast, rapid, and in‐depth analysis of large sample sets. This microfluidic CZE‐MS device, the 908 Devices ZipChip, involves minimal sample preparation and is ideal for small cation analytes, such as alkaloids. Here, we evaluated the microfluidic device for the analysis of alkaloids from Lobelia cardinalis hairy root cultures. Extracts from wild‐type, transgenic, and selected mutant plant cultures were analyzed and data batch processed using the mass spectral processing software MZmine2 and the statistical software Prism 8. In total 139 features were detected as baseline resolved peaks via the MZmine2 software optimized for the electrophoretic separations. Statistically significant differences in the relative abundance of the primary alkaloid lobinaline (C27H34N2), along with several putative “lobinaline‐like” molecules were observed utilizing this approach. Additionally, a method for performing both targeted and untargeted MS/MS experiments using the microfluidic device was developed and evaluated. Coupling data‐processing software with CZE‐MS data acquisition has enabled comprehensive metabolomic profiles from plant cell cultures to be constructed within a single working day.

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Synthetic and Natural Sources of the Pyridine Ring

Bailey¹,

Goe²,

Scriven³

1985

Chemistry of Heterocyclic Compounds: A Series of Monographs

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The Skeletal Structure of Lobinaline¹

Cited by 15 publications

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Novel multifunctional pharmacology of lobinaline, the major alkaloid from Lobelia cardinalis

Novel multifunctional pharmacology of lobinaline, the major alkaloid from Lobelia cardinalis

Microfluidic capillary zone electrophoresis mass spectrometry analysis of alkaloids in Lobelia cardinalis transgenic and mutant plant cell cultures

Synthetic and Natural Sources of the Pyridine Ring

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The Skeletal Structure of Lobinaline1

Cited by 15 publications

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Novel multifunctional pharmacology of lobinaline, the major alkaloid from Lobelia cardinalis

Novel multifunctional pharmacology of lobinaline, the major alkaloid from Lobelia cardinalis

Microfluidic capillary zone electrophoresis mass spectrometry analysis of alkaloids in Lobelia cardinalis transgenic and mutant plant cell cultures

Synthetic and Natural Sources of the Pyridine Ring

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The Skeletal Structure of Lobinaline¹