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Method for constructing curcuminoid SULTs metabolism finger-print and application

The technology of a metabolic fingerprint and a construction method is applied in the construction of the fingerprint of curcumin compound sulfonation binding reaction and the construction of the metabolic fingerprint of drug metabolizing enzymes, which can solve the difficulty in the development and application of new drugs of curcumin compounds, and the oral bioavailability. It can solve the problems of low degree and weak absorption of drug metabolism, etc., and achieve the effect of good ionization effect, good UV absorption characteristics and high sensitivity.

Inactive Publication Date: 2015-08-26
中国医科大学
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the weak absorption and rapid drug metabolism of this type of compound in the body lead to extremely low oral bioavailability, which also causes great difficulties for the development of new drugs and the wide application of curcuminoids in clinical practice.

Method used

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  • Method for constructing curcuminoid SULTs metabolism finger-print and application
  • Method for constructing curcuminoid SULTs metabolism finger-print and application
  • Method for constructing curcuminoid SULTs metabolism finger-print and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] The reaction system of SULT1A3 catalyzing CUR sulfonation binding reaction, and the metabolic activity of SULT1A3 catalyzing CUR obtained by the method.

[0038] (1) Establishment of chromatographic quantitative analysis method for CUR and its sulfonated reaction metabolites: WATERS UPLC-HCLASS instrument; diode array detector PDA; ACQUITY BEH C 18 (1.7μm2.1×50mm) chromatographic column; mobile phase is 2.5mMpH6.5 ammonium acetate aqueous solution (A)-acetonitrile (B), gradient elution: 0min, 10%B; 0-2.0min, 10~40%B ;2.0-3.0min, 40~60%B; 3.0-3.5min, 60~70%B; 3.5-4.5min, 70~90%B; 4.5-5.0min, 90%B; 5.0-5.5min, 90%B ~10%B. The internal standard is estradiol; the flow rate is 0.25ml / min; the column temperature is 35°C; the detection wavelength of CUR is 430nm, and the internal standard detection wavelength is 280nm.

[0039] (2) Enzyme reaction: Prepare three different concentrations of CUR, namely 1.25 μM, 5 μM, and 20 μM. In the incubation reaction system, use pH 7.4 ...

Embodiment 2

[0043] A reaction system in which SULT1E1 catalyzes the sulfonation reaction of DMC, and the metabolic activity of SULT1E1 catalyzed DMC obtained by the method.

[0044](1) Establishment of chromatographic quantitative analysis method for DMC and its sulfonated reaction metabolites: WATERS UPLC-HCLASS instrument; diode array detector PDA; ACQUITY BEH C18 (1.7μm2.1×50mm) chromatographic column; mobile phase is 2.5mM pH6.5 ammonium acetate aqueous solution (A)-acetonitrile (B), gradient elution is the same as CUR; internal standard is estradiol; flow rate is 0.25ml / min; the column temperature is 35°C; the DMC detection wavelength is 430nm, and the internal standard detection wavelength is 280nm.

[0045] (2) Enzyme reaction: This reaction system is similar to CUR: the three concentrations of DMC are 1.25 μM, 5 μM, and 20 μM, and SULT1E1 (final concentration is 0.00125-0.00248 mg / ml) is selected. Incubate in KPI buffer system, the reaction temperature is 37°C; the reaction tim...

Embodiment 3

[0049] The reaction system of SULT1A2 catalyzing the sulfonation binding reaction of BDMC, and the metabolic activity of SULT1E1 catalyzing BDMC obtained by the method.

[0050] (1) Establishment of chromatographic quantitative analysis method for BDMC and its sulfonated reaction metabolites: WATERS UPLC-HCLASS instrument; diode array detector PDA; ACQUITY BEH C18 (1.7μm2.1×50mm) chromatographic column; mobile phase is 2.5mM pH6.5 ammonium acetate aqueous solution (A)-acetonitrile (B), gradient elution is the same as CUR; internal standard is estradiol; flow rate is 0.25ml / min; the column temperature is 35°C; the detection wavelength of BDMC is 430nm, and the detection wavelength of internal standard is 280nm.

[0051] (2) Enzyme reaction: The reaction system is similar to CUR: three concentrations of BDMC are 1.25 μM, 5 μM, 20 μM, SULT1A2 (final concentration is 0.0093 mg / ml), in KPI buffer liquid with cofactor PAPS at pH 8.5 Incubate in the system, the reaction temperatur...

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Abstract

The invention provides a method for constructing a curcuminoid SULTs metabolism finger-print and an application. The method provided by the invention comprises the steps of: choosing and recombining SULTs, and catalyzing the sulfonated conjugation reaction of the curcuminoid by virtue of the in vitro incubation system thereof. The biological activity thereof is obtained through quantitatively determining the production of a conjugation product or the eliminated amount of a substrate within unit time, and the SULTs finger-print is established. The method establishes the finger-print of the sulfonated metabolic reaction of the SULTs mediate curcuminoid, and supplements the relevant technology of the finger-print in the field for the first time. The finger-print obtained can be used to describe and predict the in vivo and in vitro drug metabolism properties of the curcuminoid, is conducive to expounding the mechanisms such as the detoxifying ways of such compound, the drug interaction and the like, and provides both theoretical basis for development of new drugs of such drugs and scientific guidance for safe, reasonable and effective use of such drugs clinically.

Description

technical field [0001] The invention relates to a method for constructing a metabolic fingerprint of a drug-metabolizing enzyme and its application, in particular to a method for constructing a fingerprint of a curcumin compound sulfonation binding reaction catalyzed by SULTs and its application. It belongs to the field of medical technology. Background technique [0002] Curcuminoids are a class of main active ingredients extracted from plants of the genus Curcuma in the family Zingiberaceae. The main sources are commonly used traditional Chinese medicines such as turmeric, zedoary, and turmeric. A number of studies have shown that curcuminoids have good pharmacological effects in the treatment of cancer, immune deficiency, cardiovascular disease, Alzheimer's disease, diabetes, arthritis, Crohn's disease and ulcerative colitis. The core of curcuminoids is diphenylheptanedione, which can be divided into phenolic and non-phenolic types according to whether there is a hydroxy...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/48
Inventor 孟胜男吕晓玥蒋昆谕张懋璠周一平周昱马颖林王欣
Owner 中国医科大学
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