Chapter 1 The Bisbenzylisoquinoline Alkaloids

Buck, K.

doi:10.1016/s0099-9598(08)60206-0

Cited by 10 publications

(15 citation statements)

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“…Other bis(benzylisoquino1ine) alkaloids have been reported which differ in substitutions about the basic ring structures and in stereochemistry at the two chiral centers [for a review, see Buck (1987)]. Representative compounds from four conformational classes of bis(benzylisoquino1ine) analogs of tetrandrine with a+, &a, a+, and &pstereochemistry were characterized for inhibiton of 4sCa2+ uptake through L-type Ca2+ channels in GH3 cells and for their effects on the binding of ligands at each of the four sites in the CEB receptor complex present in purified porcine cardiac sarcolemmal membranes.…”

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confidence: 99%

Bis(benzylisoquinoline) analogs of tetrandrine block L-type calcium channels: Evidence for interaction at the diltiazem-binding site

Felix

King²,

Shevell³

et al. 1992

Biochemistry

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Bis(benzylisoquinoline) alkaloids block Ca2+ uptake through the L-type Ca2+ channel and modulate binding of ligands to four distinct sites (dihydropyridine, benzothiazepine, aralkylamine, and (diphenylbutyl)piperidine) in the Ca2+ entry blocker receptor complex of the channel. These alkaloids are structural analogs of tetrandrine, which has previously been demonstrated to block the L-type Ca2+ channel through interaction at the benzothiazepine (diltiazem) site (King et al., 1988). Different alkaloid conformational classes display either alpha-beta, beta-alpha, alpha-alpha, or beta-beta stereochemistry at the two chiral isoquinoline carbons. Compounds from all four classes were tested for their ability to interact with Ca2+ entry blocker ligands. All analogs completely inhibit diltiazem binding, but many only partially inhibit D-600 and fluspirilene binding. For dihydropyridine binding, the compounds show either stimulation or inhibition or exhibit no effect. This profile is quite different from the interaction displayed by diltiazem or tetrandrine. Scatchard analyses show effects predominantly on Kd for diltiazem, D-600, and PN200-110 binding. Representative conformers do not effect diltiazem dissociation rates but alter dissociation kinetics of ligands which bind to the other three sites. A correlation of the ability of these compounds to inhibit Ca2+ uptake through the L-type Ca2+ channel in GH3 cells exists only with their inhibition of diltiazem binding but not with inhibition of binding of ligands representing other classes of Ca2+ entry blockers. These data, taken together, indicate that a variety of bis(benzylisoquinoline) congeners act to block the L-type Ca2+ channel by binding to the benzothiazepine site on the channel.(ABSTRACT TRUNCATED AT 250 WORDS)

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Bis(benzylisoquinoline) analogs of tetrandrine block L-type calcium channels: Evidence for interaction at the diltiazem-binding site

Felix

King²,

Shevell³

et al. 1992

Biochemistry

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“…Natural products are an important source of new therapeutic agents in a drug discovery program and isoquinoline alkaloids are a rich, as well as important, source for seeking biologically-active agents. [1][2][3] The Anonaceae, Berberidaceae, Hernandiaceae, Lauraceae, Magnoliaceae, Menispermaceae, Papaveraceae, Ranunculaceae and Rutaceae families contain homodimeric classes of several hundred members of the so-called aporphine-benzylisoquinoline and bisbenzylisoquinoline alkaloids, which are derived biogenetically via phenol-oxidative coupling of each unit of aporphine and benzylisoquinoline and two units of benzylisoquinoline alkaloids, respectively. [1][2][3] Aporphine-benzylisoquinoline and bisbenzylisoquinoline alkaloids, two important dimeric classes of isoquinoline alkaloids, exert antihypertensive, antiarrhythmogenic, antianginal, antimicrobial, analgesic, neuromuscular blocking, muscle relaxant and antitumor activities.…”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3] The Anonaceae, Berberidaceae, Hernandiaceae, Lauraceae, Magnoliaceae, Menispermaceae, Papaveraceae, Ranunculaceae and Rutaceae families contain homodimeric classes of several hundred members of the so-called aporphine-benzylisoquinoline and bisbenzylisoquinoline alkaloids, which are derived biogenetically via phenol-oxidative coupling of each unit of aporphine and benzylisoquinoline and two units of benzylisoquinoline alkaloids, respectively. [1][2][3] Aporphine-benzylisoquinoline and bisbenzylisoquinoline alkaloids, two important dimeric classes of isoquinoline alkaloids, exert antihypertensive, antiarrhythmogenic, antianginal, antimicrobial, analgesic, neuromuscular blocking, muscle relaxant and antitumor activities. [1][2][3][4][5][6][7][8][9][10] Thalicarpine, northalicarpine, thalmelatine, adiantifoline and thalirevolutine, five of the ten investigated aporphinebenzylisoquinoline alkaloids exhibit antimicrobial, antitumor and hypotensive activities.…”

Section: Introductionmentioning

confidence: 99%

Electrospray Tandem Mass Spectrometry for Structural Characterization of Aporphine-Benzylisoquinoline Alkaloids

Moyer

2004

Eur J Mass Spectrom (Chichester)

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Electrospray mass spectrometry and tandem mass spectrometry techniques were utilized to elucidate the structures of ten aporphine-benzylisoquinoline alkaloids, consisting of monoether link between aporphine and benzyltetrahydroisoquinoline units, which were isolated and identified previously from a variety of Thalictrum sp. (Ranunculaceae family) based mainly on the UV, IR, CD, NMR, EI-MS, CI-MS, derivatization, and chemical degradation techniques. In this investigation, protonated molecules, [M+H]+ ions, for nine tertiary alkaloids, a molecular ion, [M+'] ion, for a quaternary alkaloid, and very intense doubly- protonated molecules, [M+2H]2+ ions (100% of relative abundance) in Q1 Scan MS spectra, and prominent as well as diagnostic product ions for structural information in the tandem MS/MS spectra were observed for all investigated alkaloids each in nanogram quantities. More than 10 microg quantities of each investigated alkaloid or other isoquinoline and aporphine analogs needed for the CI-MS, EI-MS and FAB-MS analysis from the previous studies.

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“…Tetrandrine (1) and berbamine (2) are closely related bisbenzylisoquinolines that are naturally occurring plant alkaloids [1]. The pharmacological properties of isoquinoline alkaloids range from opioid and curare effects (e.g.…”

Section: Introductionmentioning

confidence: 99%

“…Tetrandrine, isolated from the root of Stephania tetrandra, is present in the Chinese drug hanfangji and a known analgesic and antipyretic [2]. Our previous studies [3][4][5][6][7][8][9][10][11][12][13][14] on tetrandrine (1) and berbamine (2) have shown them to have potent inhibitory effects on phagocytic cells, inflammatory mediators and cytokines without significantly damaging the host's immune defence mechanisms. Specifically 1 has anti-inflammatory [3], anti-phagocytic [4], in vitro antioxidant [4] and immunosuppressive [3,5] properties.…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory activity of the isoquinoline alkaloid, tetrandrine, against established adjuvant arthritis in rats

1994

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Two isoquinoline plant alkaloids, tetrandrine (1) and berbamine (2), have been evaluated for anti-inflammatory activity in an acute paw oedema assay and in adjuvant-induced arthritis in rats. 1 but not 2 suppressed the chronic inflammation in the arthritis model but neither compound was active in the acute inflammation assay. In the adjuvant-induced polyarthritis, 1 was not effective when given at the time of inoculation (Day 0), nor just before (Day 7-10) signs of arthritis were evident. However, when given on a therapeutic dose schedule (Days 10-13) or continually (Day -1 to +14) on a prophylactic schedule, signs of arthritis including weight loss due to cachexia were significantly reduced. Given orally, 1 was considerably more potent than aspirin but not gastro-irritant and may be a promising lead for the development of a safe and effective treatment of chronic inflammatory diseases.

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Chapter 1 The Bisbenzylisoquinoline Alkaloids

Cited by 10 publications

References 294 publications

Bis(benzylisoquinoline) analogs of tetrandrine block L-type calcium channels: Evidence for interaction at the diltiazem-binding site

Bis(benzylisoquinoline) analogs of tetrandrine block L-type calcium channels: Evidence for interaction at the diltiazem-binding site

Electrospray Tandem Mass Spectrometry for Structural Characterization of Aporphine-Benzylisoquinoline Alkaloids

Anti-inflammatory activity of the isoquinoline alkaloid, tetrandrine, against established adjuvant arthritis in rats

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