On the molecular and electronic structure of matrine-type alkaloids

Galasso, V.; Asaro, Fioretta; Berti, Federico; Pergolese, Barbara; Kovač, Branka; Pichierri, Fabio

doi:10.1016/j.chemphys.2006.09.017

Cited by 39 publications

(51 citation statements)

References 58 publications

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“…11) Sophocarpine (SC) is a dehydroderivative of the bis-quinolizidine alkaloid matrine. 13) In China, it has entered clinical development as an injection solution with a superior inhibitory effect on Coxsackie B virus that should result in improved efficacy in the treatment of viral myocarditis. [14][15][16][17] The inhibitory actions of several matrine-type alkaloids on I Kr have recently been reported.…”

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HERG K+ Channel Blockade by the Novel Antiviral Drug Sophocarpine

Zhao

Fang

et al. 2008

Biological & Pharmaceutical Bulletin

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Torsade de pointes (TdP) arrhythmia is a potentially fatal form of ventricular arrhythmia that occurs under conditions in which cardiac repolarization is delayed (as indicated by prolonged QT intervals in electrocardiograph recordings).1-3) A likely mechanism for QT interval prolongation and TdP arrhythmias is blockade of the rapid component of the cardiac delayed rectifier K ϩ current (I Kr ), which is encoded by human ether-à-go-go-related gene (HERG). 1,4,5) More than 100 non-cardiovascular drugs can induce TdP arrhythmias or QT interval prolongations in electrocardiograms. [6][7][8][9] Regulatory guidelines [CPMP/986/96 (1997) and ICH S7B (2005)] recommend the use of preclinical in vivo and in vitro (in which a broad range of concentrations should be used) studies to detect the QT-prolonging effects and arrhythmogenic potential of new chemical entities. [10][11][12] The HERG assay (which tests I Kr ) is one of the recommended in vitro models for the detection of potential drug-induced long QT. 11)Sophocarpine (SC) is a dehydroderivative of the bis-quinolizidine alkaloid matrine. 13) In China, it has entered clinical development as an injection solution with a superior inhibitory effect on Coxsackie B virus that should result in improved efficacy in the treatment of viral myocarditis. [14][15][16][17] The inhibitory actions of several matrine-type alkaloids on I Kr have recently been reported. 18,19) We investigated the effects of SC on HERG-encoded K ϩ channels to assess the risk of this drug causing cardiac arrhythmia associated with QT interval prolongation.We set out to establish: (i) the effects of SC on the amplitude, concentration dependence and kinetics of currents conducted by HERG channels stably expressed in human embryonic kidney (HEK293) cells. This was done using a wholecell patch clamp method; and (ii) the effects of SC on HERG protein levels in HEK293 cells. This was achieved using Western blot analysis and immunofluorescence methods. MATERIALS AND METHODS HERG-Expressing Cell LinesExperiments were performed on HEK293 cells that stably expressed the wild-type HERG gene (provided by Professor Zhi-Guo Wang, Montreal Heart Institute, Montreal, Canada). Cells were maintained in Dulbecco's Modified Eagle's Medium (DMEM, Hyclone) supplemented with 10% (v/v) fetal calf serum (FCS, Gibco) and 200-mM geneticin (G-418, Gibco) at 37°C in a humidified atmosphere of 5% CO 2 .Sophocarpine SC (Dushun Ltd., Ningxia, China) was dissolved in deionized water to obtain a 10-mM stock solution, which was stored at Ϫ20°C.Electrophysiological Recordings HERG currents were measured using the whole-cell configuration of the patch clamp technique. 8,9,20) Heat-polished patch pipettes had final resistances of 2-4 MW when filled with a pipette solution containing (in mM): 130 KCl, 1 MgCl 2 · 6H 2 O, 10 HEPES, 5 Mg-ATP, 5 EGTA and 0.1 guanosine triphosphate (GTP) (pH 7.3 with KOH). The extracellular solution contained (in mM): 136 NaCl, 5.4 KCl, 5 HEPES, 1 MgCl 2 · 6H 2 O, 1 CaCl 2 and 10 glucose (pH 7.4 with NaOH). The f...

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HERG K+ Channel Blockade by the Novel Antiviral Drug Sophocarpine

Zhao

Fang

et al. 2008

Biological & Pharmaceutical Bulletin

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“…S1 (ESI † ). MT exhibits its characteristic absorption in water solution as a broad band in the range of 200-220 nm, which can be ascribed to the sum absorptions of n(N) → π ⁎ (C O) and n(O) → π ⁎ (C O) electron transition [40]. With increasing concentration of ct-DNA added, significant hypochromicity and red-shift could be observed.…”

Section: Uv-visible (Uv-vis) Absorption Titration Analysismentioning

confidence: 97%

Potential new inorganic antitumour agents from combining the anticancer traditional Chinese medicine (TCM) matrine with Ga(III), Au(III), Sn(IV) ions, and DNA binding studies

Chen

Mao

Liu

et al. 2011

Journal of Inorganic Biochemistry

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“…[7][8][9][10][11][12][13][14][15] More than forty matrine-type alkaloids had been isolated from Sophora plants since 1895. [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] Pharmacological studies showed that these alkaloids exhibited potent antiviral activities against hepatitis B (HBV), Coxsackie B3 (CVB3), and influenza A/Hanfang/359/95 (H3N2) viruses. 16,31 In China, some matrine-type alkaloids such as matrine and oxymatrine had been used for the treatment of hepatitis B, dysentery, pyogenic infections of the skin and trichomonas vaginitis in clinic.…”

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confidence: 99%

Dimeric Matrine-Type Alkaloids from the Roots of Sophora flavescens and Their Anti-Hepatitis B Virus Activities

Zhang

Zhan

et al. 2016

J. Org. Chem.

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Six unusual matrine-type alkaloid dimers, flavesines A-F (1-6, respectively), together with three proposed biosynthetic intermediates (7-9) were isolated from the roots of Sophora flavescens. Compounds 1-5 were the first natural matrine-type alkaloid dimers, and compound 6 represented an unprecedented dimerization pattern constructed by matrine and (-)-cytisine. Their structures were elucidated by NMR, MS, single-crystal X-ray diffraction, and a chemical method. The hypothetical biogenetic pathways of 1-6 were also proposed. Compounds 1-9 exhibited inhibitory activities against hepatitis B virus.

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On the molecular and electronic structure of matrine-type alkaloids

Cited by 39 publications

References 58 publications

HERG K+ Channel Blockade by the Novel Antiviral Drug Sophocarpine

HERG K+ Channel Blockade by the Novel Antiviral Drug Sophocarpine

Potential new inorganic antitumour agents from combining the anticancer traditional Chinese medicine (TCM) matrine with Ga(III), Au(III), Sn(IV) ions, and DNA binding studies

Dimeric Matrine-Type Alkaloids from the Roots of Sophora flavescens and Their Anti-Hepatitis B Virus Activities

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