CN106983757A - The A of cucurbitacin II medicinal usage - Google Patents
The A of cucurbitacin II medicinal usage Download PDFInfo
- Publication number
- CN106983757A CN106983757A CN201710406157.8A CN201710406157A CN106983757A CN 106983757 A CN106983757 A CN 106983757A CN 201710406157 A CN201710406157 A CN 201710406157A CN 106983757 A CN106983757 A CN 106983757A
- Authority
- CN
- China
- Prior art keywords
- dpp
- cucurbitacin
- medicinal usage
- compound
- present
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
Abstract
The present invention relates to the A of cucurbitacin II or its pharmaceutically acceptable solvate and its be used as purposes of the therapeutic agent especially as inhibitors of dipeptidyl IV.
Description
Technical field
The present invention relates to pharmaceutical technology field, specifically, it is used as dipeptidyl peptidase the present invention relates to the A of compound cucurbitacin II
The medicinal usage of enzyme IV (DPP-IV) inhibitor.
Background technology
DPP IV (IUBMB enzyme nomenclature EC.3.4.14.5) is a kind of II types memebrane protein, in the literature with a variety of
Title is referred to, including DPP4, DP4, DAP-IV, FAP β, ADCP 2, ABP
(ADAbp), bis- peptidyls of Dipeptidylaminopeptidase IV, Xaa-Pro--aminopeptidase, Gly-Pro naphthyls amidase, rear proline
(postproline) Dipeptidylaminopeptidase IV, lymphocyte antigen CD26, glycoprotein GP110, DPP IV, sweet ammonia
Acyl Prolyl iminopeptidase, glycyl Prolyl iminopeptidase, X- prolyl pipeptidyl bases aminopeptidase, pep X, HLA
CD26, glycylprolyl Dipeptidylaminopeptidase, two peptidyl-peptide hydrolases, glycylprolyl aminopeptidase, two peptidyls-
Aminopeptidase IV, DPP IV/CD26, aminoacyl-prolyl pipeptidyl base aminopeptidase, T cell triggering molecule Tp103, X-
PDAP.DPP IV is referred to herein as " DPP-IV ".
DPP-IV is a kind of non-classical serine aminopeptidase, and it is removed from the amino terminal (N- ends) of peptide and protein
Remove Xaa-Pro dipeptides.Some naturally occurring peptides are also it has been reported that the DPP-IV dependences of X-Gly or X-Ser type dipeptides are slow
Release.
The present invention relates to the change that can suppress dipeptidyl peptidase-IV (Dipeptidyl peptidase IV, DPP-IV) activity
Compound and/or pharmaceutically acceptable solvate, this kind of compound can be used for treatment diabetes, such as diabetes B, high blood
Sugar, metabolic syndrome, hyperinsulinemia, obesity, angiocardiopathy and abnormal such as atherosclerosis, cranial vascular disease, in
Pivot nervous system disease is abnormal including schizophrenia, anxiety disorder, Bipolar depression, depression, insomnia, cognitive disorder,
Gastrointestinal disease and exception, cancer, inflammation and inflammatory disease, respiratory disease and exception, skeletal muscle are abnormal, osteoporosis, more
Term symptom or exception, periodontal disease such as gingivitis, and various immunoregulatory disorders.
DPP-IV belongs to serine peptide enzyme family, belong to together the family also have DPP2, DPP8, DPP9, FAP and
POP etc..Animal model experiment result shows that such as anaemia, alopecia, decrease of platelet and splenomegaly can be caused by suppressing DPP8/9
Deng toxic reaction [Lankas GR, Leiting B, et al.Dipeptidyl peptidase IV inhibition for
the treatment of type2diabetes:potential importance of selectivity over
dipeptidyl peptidases8and9.Diabetes,2005,54:2988-2994].Therefore, for the single targets of DPP-IV
The design and significant [Bhumika DP, the ManJunath DG.Recent of exploitation for the selective depressant selected
approaches to medicinal chemistry and therapeutic potential of dipeptidyl
peptidase-4(DPP-4)inhibitors.European Journal of Medicinal Chemistry,2014,74:
574-605], this is also the difficult point and key point of new selective DPP-IV inhibitor research and development.
Therefore, this area still needs the strong selective DPP-IV inhibitors of structure novelty, activity to meet clinical treatment
Demand.
The content of the invention
DPP IV (Dipeptidyl peptidase IV, DPP-IV, CD26, EC 3.4.14.5) is a class energy
The serine protease of specific for hydrolysis polypeptide or protein N-terminal Xaa-Pro or Xaa-Ala dipeptides.DPP-IV is atypia
Serine protease, the Ser-Asp-His catalytic triads in its C-terminal region are different from typical serine protease, are backward
Arrangement.DPP-IV is II type integral membrane proteins, is distributed widely in mammal and respectively organizes.DPP-IV is small in intestines, liver, kidney near-end
Pipe, prostate, the differentiation surface epithelial cell of corpus luteum and leukocyte sub-type such as lymphocyte and Expression of Macrophages.Deposited in serum
In DPP-IV soluble protein form, its 26S Proteasome Structure and Function is identical with embrane-associated protein form but lacks hydrophobic transmembrane structure
Domain.
Diabetes B and fat attractive therapy can be turned into by suppressing DPP-IV.Although DPP-IV inhibitor energy
The sugar tolerance of diabetes B patient is effectively improved, but the half-life period of many inhibitor is shorter, or toxicity is larger.Accordingly, it would be desirable to open
Send out in pharmaceutical activity, stability, selectivity, toxicity, pharmacokinetics or medicine for characteristic more DPP-IV of advantage in terms of at least one
Inhibitor is treated for diabetes B.Therefore, the invention provides a class novel DPP-IV inhibitors.
Embodiment
Following test example is for illustrating the present invention.
A (the CAS of compound cucurbitacin II used in the present invention:58546-34-2) obtained by mm Suppliers.
Biological assessment
Test example 1
The compounds of this invention is tested DPP-IV enzyme inhibition activities：
Instrument:
ELIASA, Envision (PerkinElmer, USA)
Material:
People source DPP-IV, is obtained to be expressed using baculovirus expression system in insect cell.
Substrate, Ala-Pro-AMC.
Process:
DPP-IV can the ultraviolet excitation production of specific for hydrolysis substrate A la-Pro-AMC generations product AMC, AMC through 355nm
Fluorescent value linear change at 460nm wavelength in raw 460nm transmitting light, dynamic cooling water of units of measurement time, calculating obtains DPP4 activity.
Experiment is used as control compound using MERK-0431.
Sample DMSO dissolves, Cord blood, and concentration controls of the DMSO in final system is not influenceing detection activity
Within the scope of.
Compound MERK-0431 is that IC50 [nM] is 17.57 to DPP-IV inhibitory action.
The A of compound cucurbitacin II is 48.4% to DPP-IV inhibitory action when concentration is 20 μ g/mL.
Conclusion：The A of compound cucurbitacin II in the present invention has certain inhibitory action to DPP-IV enzymes.
The present invention can be summarized with others without prejudice to the concrete form of the spirit or essential characteristics of the present invention.Therefore, nothing
By from the point of view of which point, the embodiment above of the invention can only all be considered the description of the invention and can not limit this hair
It is bright.
Claims (1)
1. applications of the A of compound cucurbitacin II in DPP IV (DPP-IV) inhibitor medicaments are prepared.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710406157.8A CN106983757A (en) | 2017-06-02 | 2017-06-02 | The A of cucurbitacin II medicinal usage |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710406157.8A CN106983757A (en) | 2017-06-02 | 2017-06-02 | The A of cucurbitacin II medicinal usage |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106983757A true CN106983757A (en) | 2017-07-28 |
Family
ID=59421905
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710406157.8A Pending CN106983757A (en) | 2017-06-02 | 2017-06-02 | The A of cucurbitacin II medicinal usage |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106983757A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111411099A (en) * | 2020-05-14 | 2020-07-14 | 云南农业大学 | Hemsleya amabilis acetyl transferase, coding gene thereof and application of hemsleya amabilis acetyl transferase in preparation of cucurbitacin |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007269757A (en) * | 2006-03-31 | 2007-10-18 | Cci Corp | Fat cell differentiation inhibitor and medicine, quasi drug, cosmetic and food each containing the inhibitor |
-
2017
- 2017-06-02 CN CN201710406157.8A patent/CN106983757A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007269757A (en) * | 2006-03-31 | 2007-10-18 | Cci Corp | Fat cell differentiation inhibitor and medicine, quasi drug, cosmetic and food each containing the inhibitor |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111411099A (en) * | 2020-05-14 | 2020-07-14 | 云南农业大学 | Hemsleya amabilis acetyl transferase, coding gene thereof and application of hemsleya amabilis acetyl transferase in preparation of cucurbitacin |
| CN111411099B (en) * | 2020-05-14 | 2022-09-27 | 云南农业大学 | Hemsleya amabilis acetyl transferase, coding gene thereof and application of hemsleya amabilis acetyl transferase in preparation of cucurbitacin |
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Application publication date: 20170728 |