CN109020873A - With 14 α of target proteins sterol-demethylase three-dimensional structure screening compound and its preparing the application in fungicide - Google Patents
With 14 α of target proteins sterol-demethylase three-dimensional structure screening compound and its preparing the application in fungicide Download PDFInfo
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- CN109020873A CN109020873A CN201810775414.XA CN201810775414A CN109020873A CN 109020873 A CN109020873 A CN 109020873A CN 201810775414 A CN201810775414 A CN 201810775414A CN 109020873 A CN109020873 A CN 109020873A
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- piperidin
- azepan
- fungicide
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
- A01N43/46—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom rings with more than six members
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
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- Agronomy & Crop Science (AREA)
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- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
The invention discloses the compound screened with 14 α of target proteins sterol-demethylase three-dimensional structure and its preparing the application in fungicide.The present invention passes through indoor insecticide sensitivity measurement; demonstrating compound 1- [1-(3- chlorobenzene formacyl) piperidin-4-yl] azepan screened has good inhibitory activity to the main plant disease fungus Fusarium graminearum for causing gibberella saubinetii disease, and also has preferable inhibitory activity to the ash arrhizus bacteria for causing fruits and vegetables gray mold and the Target spot pathogen for causing ring rot of apple.Present invention firstly provides the prevention and control that green small molecule compound 1- [1-(3- chlorobenzene formacyl) piperidin-4-yl] azepan is applied to plant disease are screened with target proteins three-dimensional structure, market application prospect is wide.
Description
Technical field
The invention belongs to technical field of plant protection, and in particular to 14 α of target proteins sterol-demethylase three-dimensional structure
The compound of screening and its preparing the application in fungicide.
Background technique
FAO (Food and Agriculture Organization of the United Nation) (FAO) estimation, in the world the yield of crops because disease pest weeds harm caused by lose
About 40% or so (hundred million yuan of 4400-5500), the influence to trees are even more to be difficult to estimate.Pest and disease damage research is engaged in by the whole world
The loss that the work of scientist and all kinds of Technique Popularizing personnel are retrieved reaches hundred million yuan of 3000-4000.For a long time, chemical prevention one
It is directly the main means of prevention and control plant disease.A large amount of long-time services of chemical pesticide do not only result in the generation of resistance problem, and
It will cause medicament residual, kill non-target organism, pollution of ecological environment, and eventually pass through biological concentration and harm is generated to human body.
In order to solve the above problem, become with the green small molecule compound of plant pathogenic microorganisms target proteins three-dimensional structure modeling screening and ground
Study carefully hot spot.
Currently, the use of chemical bactericide being the main means for controlling the plant diseases such as wheat scab and occurring and endangering, prevent
Controlling gibberella saubinetii disease primary chemical medicament includes benzimidazole germicide (carbendazim, benomyl, probenazole, methyl Tobe
Saliva etc.), ergosterol biosynthesis inhibitor (Tebuconazole, triazolone, olefin conversion, propiconazole etc.) and new type bactericide cyanogen alkene bacterium
Ester etc..With long-term a large amount of uses of fungicide, fusarium graminearum gradually produces drug resistance, especially pathogen to medicament
Multi-drug resistance (muitidrug resistance, MDR), it has also become the most intractable is asked during wheat scab prevention and treatment
Topic.Therefore, fusarium graminearum multi-drug resistance mechanism, targeted developing new drug and the rational use of medicines are studied, is current agricultural
One of with the research hotspot of medical field.
In recent years, the problems such as environmental security has caused the concern of people from all walks of life, the pollution of environment, residual and drug resistance
People are made to produce very big interest to green small molecule compound.Therefore, agriculture sustainable development needs a kind of new, peace
Complete control of plant disease measure is realized.Under this overall situation, there is an urgent need to novel, environmentally protective fungicide by people
Exploitation and effective use.
Summary of the invention
The object of the present invention is to provide with target proteins sterol 14 α-demethylase three-dimensional structure screening compound and
It is preparing the application in fungicide.Present invention firstly provides screen green small molecule compound with target proteins three-dimensional structure
1- [1- (3- chlorobenzene formacyl) piperidin-4-yl] azepan is applied to the prevention and control of plant disease.
For achieving the above object, the present invention is achieved by the following scheme:
The present invention provides with 14 α of target proteins sterol-demethylase three-dimensional structure screening compound, the compound
For 1- [1- (3- chlorobenzene formacyl) piperidin-4-yl] azepan.
It is further: the molecular formula of 1- [1- (3- chlorobenzene formacyl) piperidin-4-yl] azepan:
C18H26ClN2O+, molecular weight: 321.869, structural formula is as follows:
The present invention also provides the compounds to prepare the application in the fungicide for preventing and treating phytopathogen.
Further: the phytopathogen is Fusarium graminearum, ash arrhizus bacteria and Botryosphaeria berengeriana f. sp.
It is further: 1- [1- (3- chlorobenzene formacyl) piperidin-4-yl] use of the azepan in fungicide
Concentration is 0.5mM-1mM.
It is further: 1- [1- (3- chlorobenzene formacyl) piperidin-4-yl] suppression of the azepan to Fusarium graminearum
Rate processed is 15%-25%.
It is further: 1- [1- (3- chlorobenzene formacyl) piperidin-4-yl] inhibition of the azepan to ash arrhizus bacteria
Rate is 7%-14%.
Further: 1- [1- (3- chlorobenzene formacyl) piperidin-4-yl] azepan is to Botryosphaeria berengeriana f. sp
Inhibiting rate is 13%-30%.
Compared with prior art, advantages of the present invention and have the technical effect that the present invention is based on Fusarium graminearum CYP51B eggs
White (14 α of sterol-demethylase (CYP51)) three-dimensional structure modeling screening has synthesized small molecule compound [1- (3- chlorobenzoyl
Base) piperidin-4-yl] azepan, the present invention passes through indoor insecticide sensitivity measurement, it was demonstrated that 1- [1- (3- chlorobenzoyl
Base) piperidin-4-yl] azepan is good to causing the main plant disease fungus Fusarium graminearum of gibberella saubinetii disease to have
Inhibitory activity, and also have preferably to the ash arrhizus bacteria for causing fruits and vegetables gray mold and the Target spot pathogen for causing ring rot of apple
Inhibitory activity.Present invention firstly provides screen green small molecule compound 1- [1- (3- chlorobenzoyl with target proteins three-dimensional structure
Base) piperidin-4-yl] prevention and control of the azepan applied to plant disease, solve Fusarium graminearum, ash arrhizus bacteria and ring spot
Bacterium generates resistance to various sterilization agent, causes the problem of preventive effect difference, environmentally friendly, green non-pollution meets world health group
Medicament residual toxicity standard is knitted, application prospect is had a vast market.
Detailed description of the invention
Fig. 1 is the inhibition that 1- [1- (3- chlorobenzene formacyl) piperidin-4-yl] azepan grows 3 kinds of pathogen mycelia
Effect picture.
Specific embodiment
Technical solution of the present invention is further described in detail with reference to the accompanying drawings and examples.
Embodiment 1
The present invention is based on cereal reaping hook at InterBioScreen database (https: //www.ibscreen.com/)
Bacterium CYP51B albumen (14 α of sterol-demethylase (CYP51)) three-dimensional structure modeling screens and has synthesized small molecule compound
[1- (3- chlorobenzene formacyl) piperidin-4-yl] azepan.
The English of 1- [1- (3- chlorobenzene formacyl) piperidin-4-yl] azepan are as follows: 1- [[1- (3-
CHLOROBENZOYL) PIPERIDIN-4-YL] AZEPANE, molecular formula: C18H26ClN2O+, molecular weight: 321.869, structural formula
It is as follows:
The synthesis process of 1- [1- (3- chlorobenzene formacyl) piperidin-4-yl] azepan is as follows:
Step 1:
Step 2:
1, test method
1- [1- (3- chlorobenzene formacyl) piperidin-4-yl] azepan is all made of bacterium colony to the insecticide sensitivity of pathogen
Growth rate inhibits method to be measured.Growth rate method also known as contains toxic medium method, especially suitable for do not produced on culture medium spore or
The strains tested that person's sporulation quantity is few and mycelia is closeer meets the requirement of this experiment.
Experimental implementation process is as follows:
(1) activated strains: Fusarium graminearum, ash arrhizus bacteria and the Botryosphaeria berengeriana f. sp in conservation pipe are seeded in PDA and put down
On plate, culture 3-4d is placed on spare in 4 DEG C of constant temperature refrigerators.
(2) it prepares mother liquor: weighing 0.0481g1- [1- (3- chlorobenzene formacyl) piperidin-4-yl] azepan, use solvent
DMSO (dimethyl sulfoxide) is configured to the mother liquor that concentration is 1M.
(3) the malicious plate of preparation band: PDA culture medium heating being dissolved, is cooled to 45-50 DEG C, and mother liquor is added and is made containing 0.5 He
The culture medium (dimethyl sulfoxide of respective volume is added in control) of 1mM medical fluid, is poured into cold in culture dish respectively after mixing well
But.3 repetitions are arranged in every processing.
(4) it is inoculated with pathogen: being beaten on the same circumference of colony edge of preculture with punch (diameter 6mm) and take bacterium
Cake accesses the center of malicious plate, and sealing, which is placed in 25 DEG C of constant incubators, cultivates.
2, data processing
When the colony edge of control group is close to ware wall, the colony diameter of each processing group is measured using crossing method, and
Calculate growth inhibition ratio.
3, test result
1- [1- (3- chlorobenzene formacyl) piperidin-4-yl] azepan is to Fusarium graminearum, ash arrhizus bacteria and apple wheel
The influence of line germ bacterium colony growth rate is as shown in Figure 1, the concentration and inhibiting rate of reagent agent are as shown in table 1.
Table 11- [1- (3- chlorobenzene formacyl) piperidin-4-yl] azepan makees the inhibition that 3 kinds of pathogen mycelia grow
Use measurement result
From table 1 and Fig. 1 experimental result it is found that green small molecule compound 1- [1- (3- chlorobenzene formacyl) of the present invention
Piperidin-4-yl] azepan significantly inhibits effect to Botryosphaeria berengeriana f. sp, fusarium graminearum and ash arrhizus bacteria.And
And within the scope of 0.5mM-1mM, as drug concentration increases, inhibitory effect is more obvious.
Botryosphaeria berengeriana f. sp: ring rot of apple also known as scurf, wheel line decayed fruit disease, are the weights on apple limb portion and fruit
Biological epidemics are wanted, often cause that apple limb bark is coarse, locality is downright bad and fruit rot.Illness plant fruit-setting rate is low, causes
Tree body is weak and yield is reduced, or even garden is ruined in total crop failure.In recent years, with the commerial growing of susceptible kind Fuji apple, apple
Ring spot disease incidence increases year by year, and hazard area constantly expands, it has also become the serious plant disease in Chinese apple production seriously threatens
The sustainable development of Apple Industry.
Fusarium graminearum: head blight is a kind of destructive disease, and fringe can be caused rotten, and Severe Reduction and quality is caused to drop
It is low.With the change of global warming, cropping system and mode, wheat scab constantly spreads extension, often results in wheat
The underproduction, quality reduce, and contain mycotoxin in the wheat seed infected, can cause person poultry poisoning and serious disease.The disease
Bacterium is in addition to endangering wheat, moreover it is possible to infect the grass family such as a variety of gramineous crops such as barley, oat, rice, corn and goose hat grass
Weeds, in addition, can also infect the crops such as soybean, cotton, sweet potato.
Ash arrhizus bacteria: ash arrhizus bacteria host is extensive, can infect tomato, cucumber, eggplant, Kidney bean, green pepper, celery, asparagus lettuce, lettuce
A variety of fruits and vegetables such as lettuce, grape.
The above embodiments are merely illustrative of the technical solutions of the present invention, rather than is limited；Although referring to aforementioned reality
Applying example, invention is explained in detail, for those of ordinary skill in the art, still can be to aforementioned implementation
Technical solution documented by example is modified or equivalent replacement of some of the technical features；And these are modified or replace
It changes, the spirit and scope for claimed technical solution of the invention that it does not separate the essence of the corresponding technical solution.
Claims (8)
1. with 14 α of target proteins sterol-demethylase three-dimensional structure screening compound, it is characterised in that the compound is 1-
[1-(3- chlorobenzene formacyl) piperidin-4-yl] azepan.
2. it is according to claim 1 with 14 α of target proteins sterol-demethylase three-dimensional structure screening compound, it is special
Sign is: the molecular formula of the 1- [1-(3- chlorobenzene formacyl) piperidin-4-yl] azepan: C18H26ClN2O+, molecule
Amount: 321.869, structural formula is as follows:
。
3. compound as claimed in claim 2 is preparing the application in the fungicide for preventing and treating phytopathogen.
4. compound according to claim 2 is preparing the application in the fungicide for preventing and treating phytopathogen, special
Sign is: the phytopathogen is Fusarium graminearum, ash arrhizus bacteria and Botryosphaeria berengeriana f. sp.
5. compound according to claim 2 is preparing the application in the fungicide for preventing and treating phytopathogen, special
Sign is: the 1- [1-(3- chlorobenzene formacyl) piperidin-4-yl] the use concentration of azepan in fungicide is
0.5mM-1mM。
6. compound according to claim 5 is preparing the application in the fungicide for preventing and treating phytopathogen, special
Sign is: the 1- [1-(3- chlorobenzene formacyl) piperidin-4-yl] azepan is 15%- to the inhibiting rate of Fusarium graminearum
25%。
7. compound according to claim 5 is preparing the application in the fungicide for preventing and treating phytopathogen, special
Sign is: the 1- [1-(3- chlorobenzene formacyl) piperidin-4-yl] azepan is 7 %- to the inhibiting rate of ash arrhizus bacteria
14%。
8. compound according to claim 5 is preparing the application in the fungicide for preventing and treating phytopathogen, special
Sign is: the 1- [1-(3- chlorobenzene formacyl) piperidin-4-yl] azepan is to the inhibiting rate of Botryosphaeria berengeriana f. sp
13%-30%。
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| CN201810775414.XA CN109020873B (en) | 2018-07-16 | 2018-07-16 | Compound screened by three-dimensional structure of target protein sterol 14 α -demethylase and application thereof in preparation of bactericide |
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| CN201810775414.XA CN109020873B (en) | 2018-07-16 | 2018-07-16 | Compound screened by three-dimensional structure of target protein sterol 14 α -demethylase and application thereof in preparation of bactericide |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113287620A (en) * | 2021-06-18 | 2021-08-24 | 浙江大学 | Application of 1H-pyrazolo [3,4-d ] pyrimidine compound in preparation of fusarium graminearum bactericide |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1447808A (en) * | 2000-07-17 | 2003-10-08 | 兰贝克赛实验室有限公司 | Oxazolidinone derivatives as anticrobials |
| CN101302217A (en) * | 2008-07-02 | 2008-11-12 | 南开大学 | Triazole compounds, preparation and use thereof |
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2018
- 2018-07-16 CN CN201810775414.XA patent/CN109020873B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1447808A (en) * | 2000-07-17 | 2003-10-08 | 兰贝克赛实验室有限公司 | Oxazolidinone derivatives as anticrobials |
| CN101302217A (en) * | 2008-07-02 | 2008-11-12 | 南开大学 | Triazole compounds, preparation and use thereof |
Non-Patent Citations (1)
| Title |
|---|
| 王沙沙: "《STN检索报告》", 19 June 2002 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113287620A (en) * | 2021-06-18 | 2021-08-24 | 浙江大学 | Application of 1H-pyrazolo [3,4-d ] pyrimidine compound in preparation of fusarium graminearum bactericide |
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