Structural significance of azaheterocyclic amines related to Parkinson's disease for dopamine transporter

Matsubara, Kazuo; Senda, Tomoko; Uezono, Takumi; Fukushima, S; Ohta, Shigeru; Igarashi, Kazuo; Naoi, Makoto; Yamashita, Yasunori; Ohtaki, Ko-ichi; Hayase, Nobumasa; Akutsu, Shigetaka; Kimura, Kojiro

doi:10.1016/s0014-2999(98)00131-9

Cited by 32 publications

(24 citation statements)

References 36 publications

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“…Harman (2) and norharman (1) were comutagens or precursors of mutagens; TaClo (21), TaBro (68) and N-methylated -carboline derivatives were potent endogenous neurotoxins; and N-nitroso derivatives of -carboline and APNH (25) derivatives were endogenous mutagens and carcinogens. On the other hand, human are continuously exposed to endogenous and exogenouscarboline alkaloids.…”

Section: Discussionmentioning

confidence: 99%

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β-Carboline Alkaloids: Biochemical and Pharmacological Functions

Cao

Peng²,

Wang³

et al. 2007

CMC

617

353

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beta-Carboline alkaloids are a large group of natural and synthetic indole alkaloids with different degrees of aromaticity, some of which are widely distributed in nature, including various plants, foodstuffs, marine creatures, insects, mammalians as well as human tissues and body fluids. These compounds are of great interest due to their diverse biological activities. Particularly, these compounds have been shown to intercalate into DNA, to inhibit CDK, Topisomerase, and monoamine oxidase, and to interact with benzodiazepine receptors and 5-hydroxy serotonin receptors. Furthermore, these chemicals also demonstrated a broad spectrum of pharmacological properties including sedative, anxiolytic, hypnotic, anticonvulsant, antitumor, antiviral, antiparasitic as well as antimicrobial activities. In this review, we summerized the biochemical and pharmacological functions of beta-carboline alkaloids.

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Section: Discussionmentioning

confidence: 99%

“…N-methylated -carbolinium ions ( C+) are substrates for the dopamine transporter [68][69], and are potent inhibitors of mitochondrial respiration [70][71]. C+ is postulated to interact with specific cellular targets such as various proteins [110].…”

Section: Interaction With Enzymatic Systemsmentioning

confidence: 99%

β-Carboline Alkaloids: Biochemical and Pharmacological Functions

Cao

Peng²,

Wang³

et al. 2007

CMC

617

353

View full text Add to dashboard Cite

show abstract

“…1993), and transmembrane transportation via the DAT (Drucker et al . 1990; Matsubara et al . 1998b).…”

Section: Discussionmentioning

confidence: 99%

Dopamine transporter‐mediated cytotoxicity of β‐carbolinium derivatives related to Parkinson's disease: relationship to transporter‐dependent uptake

Storch

Hwang

Gearhart

et al. 2004

Journal of Neurochemistry

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Endogenous or exogenous b-carboline (bC) derivatives structurally related to the selective dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its active metabolite 1-methyl-4-phenylpyridinium (MPP + ) may contribute to dopaminergic neurodegeneration in Parkinson's disease (PD). We addressed the importance of the dopamine transporter (DAT) for selective dopaminergic toxicity by testing the differential cytotoxicity and cellular uptake of 12 bCs in human embryonic kidney HEK-293 cells ectopically expressing the DAT gene. Cell death was measured using [4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and trypan blue exclusion assays, and uptake by a fluorescence-based uptake assay.

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“…The protection of indole nitrogen atom might inhibit conversion into an electronically neutral molecule under cellular conditions (Chart 5). 38) Probably, according as the same reason, tetracyclic canthin-6-one analog 6k displayed good antiplasmodial property. Replacement of methyl group as an R 5 substituent by an ethyl group resulted in a 10-fold increase in antiplasmodial potency for 6ab (versus 6aa), but a 2-fold decrease in activity was observed for 6ce (versus 6cc).…”

Section: )mentioning

confidence: 92%

Synthesis and Evaluation of β-Carbolinium Cations as New Antimalarial Agents Based on π-Delocalized Lipophilic Cation (DLC) Hypothesis

et al. 2005

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Several b b-carbolines including naturally occurring substances and their corresponding cationic derivatives were synthesized and evaluated for antimalarial (antiplasmodial) activity in vitro and in vivo. A tetracyclic carbolinium salt was elucidated for antileishmanial and antitrypanosomal activities in vitro as well as antiplasmodial activity. Quarternary carbolinium cations showed much higher potencies in vitro than electronically neutral b b-carbolines and a good correlation was observed between p p-delocalized lipophilic cationic (DLC) structure and antimalarial efficacy. b b-Carbolinium compounds exhibit medium suppressive activity in vivo against rodent malaria.

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Structural significance of azaheterocyclic amines related to Parkinson's disease for dopamine transporter

Cited by 32 publications

References 36 publications

β-Carboline Alkaloids: Biochemical and Pharmacological Functions

β-Carboline Alkaloids: Biochemical and Pharmacological Functions

Dopamine transporter‐mediated cytotoxicity of β‐carbolinium derivatives related to Parkinson's disease: relationship to transporter‐dependent uptake

Synthesis and Evaluation of β-Carbolinium Cations as New Antimalarial Agents Based on π-Delocalized Lipophilic Cation (DLC) Hypothesis

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Structural significance of azaheterocyclic amines related to Parkinson's disease for dopamine transporter

Cited by 32 publications

References 36 publications

&#946;-Carboline Alkaloids: Biochemical and Pharmacological Functions

&#946;-Carboline Alkaloids: Biochemical and Pharmacological Functions

Dopamine transporter‐mediated cytotoxicity of β‐carbolinium derivatives related to Parkinson's disease: relationship to transporter‐dependent uptake

Synthesis and Evaluation of &beta;-Carbolinium Cations as New Antimalarial Agents Based on &pi;-Delocalized Lipophilic Cation (DLC) Hypothesis

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β-Carboline Alkaloids: Biochemical and Pharmacological Functions

β-Carboline Alkaloids: Biochemical and Pharmacological Functions

Synthesis and Evaluation of β-Carbolinium Cations as New Antimalarial Agents Based on π-Delocalized Lipophilic Cation (DLC) Hypothesis