CN101863909A - Norcantharidin derivative and activity testing method and application thereof - Google Patents

Norcantharidin derivative and activity testing method and application thereof Download PDF

Info

Publication number
CN101863909A
CN101863909A CN201010197629A CN201010197629A CN101863909A CN 101863909 A CN101863909 A CN 101863909A CN 201010197629 A CN201010197629 A CN 201010197629A CN 201010197629 A CN201010197629 A CN 201010197629A CN 101863909 A CN101863909 A CN 101863909A
Authority
CN
China
Prior art keywords
phenyl
substituted
norcantharidin
derivative
formula
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.)
Pending
Application number
CN201010197629A
Other languages
Chinese (zh)
Inventor
邓莉平
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University of Shaoxing
Original Assignee
University of Shaoxing
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by University of Shaoxing filed Critical University of Shaoxing
Priority to CN201010197629A priority Critical patent/CN101863909A/en
Publication of CN101863909A publication Critical patent/CN101863909A/en
Pending legal-status Critical Current

Links

Landscapes

  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention discloses a norcantharidin derivative and an activity testing method and an application thereof and relates to the field of cantharidin derivatives. The norcantharidin derivative has two kinds, one is a norcantharidin dimer derivative, and the other is a heterocyclic substituted norcantharidin derivative. Cell counting kit-8 is used to analyze the influence of the compound on the activity of human lung adenocarcinoma cells A549. The norcantharidin derivative has good anti-tumor activity.

Description

Norcantharidin derivative and activity test method thereof and application
Technical field:
The invention belongs to the cantharidin derivative field, more specifically relate to a kind of Norcantharidin dimer derivate and a kind of heterocyclic ring substituent norcantharidin derivative and synthetic method and application.
Background technology:
Cantharidin (cantharidin) is China's Chinese medicine among the people, is the effective ingredient of treatment malignant tumor medicine.Modern study proves that it has certain curative effect to primary hepatocarcinoma, and leukocyte increasing is arranged, and does not suppress advantages such as immunity system, therefore, has very high medicinal researching value, causes people's extensive concern.But the toxicity of Cantharidin is bigger, synthetic very complicated, recently studies show that, lacked 2 in the Norcantharidin (norcantharidin), two methyl of 3, Norcantharidin has not only kept stronger anti-tumor activity and unique function of increasing leukocyte, and toxicity reduces greatly, has eliminated Cantharidin basically the urinary system telson is swashed side effect.
Therefore, relevant with a Cantharidin backbone modification synthetic work that is significant is to remove the prosposition methyl substituted.This structural modification can not influence antitumour activity and toxicity decreases, and, make synthesis step simplify.On the other hand, the activity research progress of cantharidin derivative shows that the structure activity relationship of Cantharidin is as follows: 1) dicyclo [2.2.1] heptane is the basic framework ring of Cantharidin, and the methyl of removing on 2-C or the 3-C can not influence its activity; 1-C or 4-C go up the introducing substituting group can make its active reduction, and the cantharidin derivative that has absolute steric configuration in the 1-C position has good inhibition selectivity to PP2B; Can introduce substituting group on 5-C or the 6-C, the introducing substituting group can influence the interaction to PP1 and PP2A on the contrary on 5-C or 6-C, strengthens the inhibition to PP2B simultaneously.Also can two keys between 5-C and the 6-C; 7-oxo bridge key is must be obligato, may be the cause that Sauerstoffatom energy and PP1 and PP2A form hydrogen bond; 2) on the anhydride rings anhydride moiety also principle can lose restraining effect to PP1 and PP2A.
Retrofit work to Cantharidin structure 5-C or 6-C is generally all just introduced substituting group, but the pharmacology test result is not ideal enough.Discover that the pyrazoles Hete rocyclic derivatives also has intensive physiology and pharmacologically active, as antibiotic, effects such as spasmolytic anti-inflammatory coordinate plant growth and anti-platelet aggregation have important use in the production of medicine and agricultural chemicals.
Just under this enlightenment, obviously improve or strengthen this feature of biological activity of compound in view of different activities heterocycle focusing energy in a part, and bioisostere principle, we design to synthesize in Norcantharidin substituted aromatic amines structure and carry out 1 on the two keys of 5-C and 6-C, 3[3+2] dipole cycloaddition introducing five-membered ring pyrazoles ring and pyrazoles ring, obtain a series of norcantharidin derivatives.
Summary of the invention:
The objective of the invention is to disclose a kind of norcantharidin derivative, specifically be meant Norcantharidin dimer derivate and a kind of heterocyclic ring substituent norcantharidin derivative and intermediate thereof.
Another object of the present invention is to provide the activity test method and the result of these two kinds of norcantharidin derivatives.
The technical solution used in the present invention is as follows:
An a kind of Norcantharidin dimer derivate wherein class is the Norcantharidin dimer derivate of Han isoxazole ring.Its general structure as shown in Equation 1.
Figure BSA00000157372800021
Formula 1
In the formula 1:
R 1For to the fluorine substituted-phenyl, to the chlorine substituted-phenyl, to methylsulfonyl substituted-phenyl, 1-hydroxyl-2-methoxyl group substituted-phenyl or benzo [1,3] dioxa cyclopentenyl.
The another kind of of a kind of Norcantharidin dimer derivate is the Norcantharidin dimer derivate that contains the pyrazoles ring.Its general structure as shown in Equation 2.
Formula 2
In the formula 2:
R 2Be phenyl, adjacent chlorine substituted-phenyl, 2,3-dichloro substituted-phenyl, 2-phenyl-2H-1,2,3-triazole-4-substituting group or quinoxaline-2-substituting group.
An a kind of heterocyclic ring substituent norcantharidin derivative wherein class is the heterocyclic ring substituent norcantharidin derivative of Han isoxazole ring.Its general structure as shown in Equation 3.
Figure BSA00000157372800023
Formula 3
In the formula 3:
R 1Be H or methyl;
R 2For to the fluorine substituted-phenyl, to the chlorine substituted-phenyl, to methylsulfonyl substituted-phenyl, 1-hydroxyl-2-methoxyl group substituted-phenyl or benzo [1,3] dioxa cyclopentenyl.
A kind of another kind of heterocyclic ring substituent norcantharidin derivative that contains the pyrazoles ring of heterocyclic ring substituent norcantharidin derivative.Its general structure as shown in Equation 4.
Figure BSA00000157372800031
Formula 4
In the formula 4:
R 1Be H or methyl;
R 3Be phenyl, adjacent chlorine substituted-phenyl, 2,3-dichloro substituted-phenyl, 2-phenyl-2H-1,2,3-triazole-4-substituting group or quinoxaline-2-substituting group.
The present invention also provides the activity test method of above-mentioned two kinds of norcantharidin derivatives, may further comprise the steps:
(1), the A549 cell cultivated is centrifugal after with trysinization, with new substratum suspend again the back with liquid subpackage instrument mutidrop in each hole of 384 orifice plates with 300 A549 cells of 50ul volume plantation;
(2), at 37 ℃, 5%CO 2After cultivating 24h under the condition, stimulate with automatic fluid treatment system Bravo packing medicine, the concentration of treatment of all cpds has: 16uM 8uM4uM 2uM 1uM 0.5uM 0.25uM 0.125uM, and every kind of processing has four repetitions;
(3), after step 2 is handled 48h, detect with the activity of CCK-8 test kit pair cell: every hole adding 5ul CCK-8 solution, read the absorption value of each hole wavelength with microplate reader at the 450nm place; In cell culture incubator, continue to hatch 100min, read the absorption value of wavelength once more at the 450nm place with microplate reader.The changing value of getting twice absorption value changes divided by the absorption value that does not add the compound treatment hole, gets every group of four multiple mean values and is hole inner cell activity.The inhibition efficient of compound pair cell=1-hole inner cell activity will input to http://bsmdb.tmd.ac.jp:3000/cbdb/ic50 according to the gradient of compound concentration and cytoactive, calculate finally to obtain IC50.
The present invention also provides above-mentioned two kinds of cantharidin derivative application on synthesizing antineoplastic medicament.
Compared with prior art, the present invention has following beneficial effect:
This is the plain imide derivative of a kind of novel N-substituted dehydronorcantharidiimide, and it is introduced five-membered ring isoxazole ring and pyrazoles ring in the cantharidin derivative structure, and has good antineoplastic activity.
The invention will be further described below in conjunction with embodiment.
Embodiment:
Following embodiment further specifies the present invention, and only is used to illustrate the present invention, and does not constitute
Limitation of the present invention.The experiment test object is as shown in table 1.
Table 1: experiment test object
Figure BSA00000157372800041
Figure BSA00000157372800051
Figure BSA00000157372800061
Figure BSA00000157372800071
Figure BSA00000157372800081
Embodiment 1: analyze these 32 kinds of compounds to the active influence of human lung adenocarcinoma cell A549 with cell counting kit-8.
(1) the A549 cell cultivated is centrifugal after with trysinization, with new substratum suspend again the back with liquid subpackage instrument mutidrop in each hole of 384 orifice plates with 300 A549 cells of 50ul volume plantation;
(2) at 37 ℃, 5%CO 2After cultivating 24h under the condition, stimulate with automatic fluid treatment system Bravo packing medicine, the concentration of treatment of all cpds has: 16uM 8uM4uM 2uM 1uM 0.5uM 0.25uM 0.125uM, and every kind of processing has four repetitions;
(3) behind the 48h, detect with the activity of CCK-8 test kit pair cell: every hole adds 5ul CCK-8 solution, reads the absorption value of each hole wavelength at the 450nm place with microplate reader; In cell culture incubator, continue to hatch 100min, read the absorption value of wavelength once more at the 450nm place with microplate reader.The changing value of getting twice absorption value changes divided by the absorption value that does not add the compound treatment hole, gets every group of four multiple mean values and is hole inner cell activity.The inhibition efficient of compound pair cell=1-hole inner cell activity will input to http://bsmdb.tmd.ac.ip:3000/cbdb/ic50 according to the gradient of compound concentration and cytoactive, calculate finally to obtain IC50.
Detected result is as shown in table 2: 31 couples of A549 of compound have certain inhibition effect, have almost completely suppressed the growth of A549 cell under the concentration of 16uM, 32uM, 64uM, IC 50Calculation result be 4.037uM.All the other compounds are not very obvious to the restraining effect of A549.
Table 2: remaining cell viability behind the compound treatment cell 48h of different concns
??Drug??\uM ??64 ??32 ??16 ??8 ??4 ??2 ??1 ??0.5
??1 ??average ??-6.14％ ??-14.42％ ??2.83％ ??-1.58％ ??-2.58％ ??-4.67％ ??-13.38％ ??-1.17％
??SD± ??5.60％ ??7.29％ ??8.68％ ??10.59％ ??4.86％ ??3.51％ ??5.16％ ??8.32％
??2 ??average ??7.17％ ??-0.46％ ??-14.59％ ??-15.34％ ??-6.12％ ??-3.67％ ??-3.13％ ??-3.88％
??SD± ??6.66％ ??9.62％ ??5.63％ ??3.78％ ??6.98％ ??3.98％ ??6.13％ ??4.72％
??3 ??average ??40.65％ ??-6.31％ ??-0.25％ ??-2.84％ ??-8.78％ ??-0.43％ ??-15.15％ ??3.48％
??SD± ??6.75％ ??7.66％ ??5.19％ ??7.99％ ??6.61％ ??6.23％ ??3.98％ ??4.18％
??4 ??average ??1.21％ ??8.75％ ??11.01％ ??1.49％ ??-10.82％ ??1.66％ ??2.82％ ??0.60％
??SD± ??3.02％ ??4.45％ ??5.91％ ??5.37％ ??5.59％ ??9.20％ ??3.32％ ??8.30％
??5 ??average ??17.27％ ??9.89％ ??10.78％ ??6.41％ ??-1.89％ ??5.29％ ??10.86％ ??-3.72％
??SD± ??4.14％ ??5.84％ ??6.75％ ??9.43％ ??5.19％ ??10.95％ ??2.67％ ??6.23％
??6 ??average ??6.19％ ??7.50％ ??-4.29％ ??-9.05％ ??-1.13％ ??-1.53％ ??1.03％ ??8.25％
??SD± ??3.41％ ??5.08％ ??7.83％ ??4.99％ ??5.32％ ??5.93％ ??6.60％ ??3.53％
??Drug??\uM ??64 ??32 ??16 ??8 ??4 ??2 ??1 ??0.5
??7 ??average ??1.03％ ??-4.56％ ??-2.08％ ??1.19％ ??4.12％ ??-3.65％ ??-9.90％ ??-4.68％
??SD± ??0.97％ ??7.93％ ??7.27％ ??5.27％ ??10.37％ ??7.43％ ??5.20％ ??3.12％
??8 ??average ??0.59％ ??-6.39％ ??-21.03％ ??-12.81％ ??-13.07％ ??-15.53％ ??-15.42％ ??-2.47％
??SD± ??3.44％ ??6.03％ ??6.37％ ??5.73％ ??6.84％ ??2.93％ ??1.28％ ??4.30％
??9 ??average ??11.71％ ??-12.85％ ??-4.29％ ??-0.67％ ??-2.16％ ??-1.47％ ??-6.94％ ??-5.75％
??SD± ??5.21％ ??11.40％ ??1.92％ ??7.81％ ??10.44％ ??6.08％ ??2.31％ ??2.28％
??10 ??average ??-7.43％ ??19.18％ ??7.40％ ??-0.13％ ??0.62％ ??-3.52％ ??-10.69％ ??10.82％
??SD± ??4.21％ ??4.25％ ??4.99％ ??4.31％ ??5.01％ ??5.15％ ??8.91％ ??10.10％
??11 ??average ??22.57％ ??-2.33％ ??8.31％ ??7.11％ ??5.68％ ??-1.35％ ??4.71％ ??0.80％
??SD± ??4.12％ ??6.12％ ??6.02％ ??6.05％ ??7.29％ ??6.78％ ??2.21％ ??8.82％
??12 ??average ??5.71％ ??19.83％ ??-2.70％ ??-3.62％ ??-1.13％ ??8.95％ ??-2.83％ ??7.01％
??SD± ??4.96％ ??7.79％ ??1.77％ ??8.27％ ??4.07％ ??5.51％ ??8.37％ ??3.35％
??Drug??\uM ??64 ??32 ??16 ??8 ??4 ??2 ??1 ??0.5
??13 ??average ??-7.89％ ??-9.84％ ??13.20％ ??0.26％ ??5.02％ ??-13.86％ ??-18.76％ ??-12.84％
??SD± ??3.04％ ??4.20％ ??1.91％ ??5.41％ ??7.56％ ??6.23％ ??5.88％ ??5.61％
??14 ??average ??52.07％ ??22.24％ ??-25.06％ ??-21.18％ ??0.14％ ??-24.25％ ??-17.93％ ??-4.42％
??SD± ??9.68％ ??8.12％ ??3.65％ ??7.63％ ??6.51％ ??6.55％ ??3.51％ ??5.44％
??15 ??average ??39.87％ ??-4.35％ ??-11.92％ ??-15.15％ ??-18.78％ ??-12.99％ ??-21.48％ ??-20.28％
??SD± ??3.73％ ??6.74％ ??7.43％ ??5.21％ ??3.41％ ??4.17％ ??4.70％ ??5.37％
??16 ??average ??34.65％ ??23.65％ ??13.61％ ??-0.47％ ??-18.65％ ??-11.42％ ??-3.88％ ??-3.13％
??SD± ??5.29％ ??2.65％ ??3.84％ ??5.07％ ??3.39％ ??5.04％ ??7.68％ ??8.00％
??17 ??average ??21.60％ ??-7.92％ ??-2.98％ ??11.78％ ??4.34％ ??7.23％ ??-16.03％ ??-9.39％
??SD± ??9.41％ ??3.20％ ??4.08％ ??3.09％ ??3.73％ ??5.57％ ??4.40％ ??5.39％
??18 ??average ??20.00％ ??4.28％ ??-18.39％ ??-6.74％ ??-20.26％ ??12.45％ ??-10.73％ ??1.26％
??SD± ??1.87％ ??5.58％ ??3.20％ ??1.60％ ??6.81％ ??59.03％ ??4.70％ ??3.95％
??Drug??\uM ??64 ??32 ??16 ??8 ??4 ??2 ??1 ??0.5
??19 ??average ??9.10％ ??-0.83％ ??-16.04％ ??-19.56％ ??-6.63％ ??-9.26％ ??-11.09％ ??-2.03％
??SD± ??4.30％ ??4.39％ ??5.46％ ??3.63％ ??2.40％ ??3.41％ ??2.64％ ??7.23％
??20 ??average ??42.64％ ??12.76％ ??-2.15％ ??-14.02％ ??-4.25％ ??1.65％ ??-3.87％ ??-6.28％
??SD± ??2.04％ ??6.64％ ??7.24％ ??7.91％ ??8.17％ ??10.59％ ??3.42％ ??6.15％
??21 ??average ??13.72％ ??1.82％ ??15.31％ ??20.15％ ??12.25％ ??-2.12％ ??-12.49％ ??13.71％
??SD± ??4.58％ ??10.08％ ??14.65％ ??8.26％ ??10.16％ ??3.05％ ??3.00％ ??16.72％
??22 ??average ??57.80％ ??11.04％ ??7.72％ ??7.66％ ??2.70％ ??3.44％ ??-10.69％ ??-8.90％
??SD± ??5.58％ ??5.19％ ??9.81％ ??11.19％ ??8.93％ ??2.44％ ??1.98％ ??8.34％
??23 ??average ??-2.28％ ??15.63％ ??-8.65％ ??8.41％ ??-3.04％ ??-1.31％ ??-9.59％ ??-6.25％
??SD± ??3.04％ ??7.63％ ??3.11％ ??8.83％ ??4.07％ ??1.96％ ??5.26％ ??4.13％
??24 ??average ??-0.53％ ??-3.10％ ??-14.33％ ??-4.14％ ??-11.85％ ??0.09％ ??-2.03％ ??6.48％
??SD± ??6.58％ ??5.94％ ??4.39％ ??6.56％ ??3.87％ ??9.98％ ??3.29％ ??8.42％
??Drug??\uM ??64 ??32 ??16 ??8 ??4 ??2 ??1 ??0.5
??25 ??average ??13.56％ ??-8.28％ ??13.20％ ??-10.28％ ??-9.47％ ??-6.64％ ??3.68％ ??-16.93％
??SD± ??10.34％ ??10.76％ ??4.72％ ??3.29％ ??6.54％ ??2.26％ ??5.55％ ??9.20％
??26 ??average ??15.46％ ??8.70％ ??-14.50％ ??17.54％ ??14.31％ ??11.48％ ??-12.63％ ??-1.66％
??SD± ??5.56％ ??3.91％ ??1.57％ ??9.14％ ??3.28％ ??6.95％ ??9.30％ ??5.55％
??27 ??average ??77.23％ ??14.98％ ??5.95％ ??23.46％ ??3.33％ ??7.06％ ??-18.88％ ??3.23％
??SD± ??0.62％ ??4.54％ ??6.21％ ??2.03％ ??7.55％ ??7.92％ ??5.02％ ??2.34％
??28 ??average ??-4.12％ ??15.90％ ??17.62％ ??12.67％ ??-11.34％ ??2.89％ ??-6.22％ ??2.86％
??SD± ??9.67％ ??4.53％ ??1.88％ ??7.04％ ??10.95％ ??8.08％ ??3.47％ ??2.38％
??29 ??average ??7.54％ ??11.69％ ??11.36％ ??-1.17％ ??20.39％ ??-2.42％ ??-5.73％ ??-2.02％
??SD± ??3.15％ ??4.69％ ??3.44％ ??6.69％ ??5.59％ ??4.81％ ??10.89％ ??5.03％
??30 ??average ??43.84％ ??11.47％ ??8.78％ ??9.75％ ??-14.97％ ??-0.34％ ??0.87％ ??17.58％
??SD± ??2.38％ ??6.11％ ??4.13％ ??5.88％ ??10.00％ ??1.65％ ??9.95％ ??5.34％
??Drug??\uM ??64 ??32 ??16 ??8 ??4 ??2 ??1 ??0.5
??31 ??average ??101.48％ ??99.75％ ??100.26％ ??50.71％ ??-14.68％ ??-1.43％ ??-8.56％ ??-20.40％
??SD± ??0.85％ ??1.56％ ??1.62％ ??10.17％ ??8.52％ ??4.35％ ??4.82％ ??4.59％
??32 ??average ??13.25％ ??-3.23％ ??-13.84％ ??19.00％ ??16.83％ ??15.08％ ??-12.29％ ??-15.06％
??SD± ??5.14％ ??4.15％ ??3.16％ ??5.23％ ??4.01％ ??3.32％ ??6.56％ ??9.60％

Claims (6)

1. a norcantharidin derivative is characterized in that, its structure Norcantharidin dimer derivate that contains isoxazole ring as shown in Equation 1
Figure FSA00000157372700011
Formula 1
In the formula 1:
R 1For to the fluorine substituted-phenyl, to the chlorine substituted-phenyl, to methylsulfonyl substituted-phenyl, 1-hydroxyl-2-methoxyl group substituted-phenyl or benzo [1,3] dioxa cyclopentenyl.
2. a norcantharidin derivative is characterized in that, its structure Norcantharidin dimer derivate that contains the pyrazoles ring as shown in Equation 2
Figure FSA00000157372700012
Formula 2
In the formula 2:
R 2Be phenyl, adjacent chlorine substituted-phenyl, 2,3-dichloro substituted-phenyl, 2-phenyl-2H-1,2,3-triazole-4-substituting group or quinoxaline-2-substituting group.
3. a norcantharidin derivative is characterized in that, its structure heterocyclic ring substituent norcantharidin derivative that contains isoxazole ring as shown in Equation 3
Figure FSA00000157372700013
Formula 3
In the formula 3:
R 1Be H or methyl;
R 2For to the fluorine substituted-phenyl, to the chlorine substituted-phenyl, to methylsulfonyl substituted-phenyl, 1-hydroxyl-2-methoxyl group substituted-phenyl or benzo [1,3] dioxa cyclopentenyl.
4. a norcantharidin derivative is characterized in that, its structure heterocyclic ring substituent norcantharidin derivative that contains the pyrazoles ring as shown in Equation 4
Figure FSA00000157372700021
Formula 4
In the formula 4:
R 1Be H or methyl;
R 3Be phenyl, adjacent chlorine substituted-phenyl, 2,3-dichloro substituted-phenyl, 2-phenyl-2H-1,2,3-triazole-4-substituting group or quinoxaline-2-substituting group.
5. the activity test method of the described norcantharidin derivative of claim 1～4 may further comprise the steps:
(1), the A549 cell cultivated is centrifugal after with trysinization, with new substratum suspend again the back with liquid subpackage instrument mutidrop in each hole of 384 orifice plates with 300 A549 cells of 50ul volume plantation;
(2), at 37 ℃, 5%CO 2After cultivating 24h under the condition, stimulate with automatic fluid treatment system Bravo packing medicine, the concentration of treatment of all cpds has: 16uM 8uM4uM 2uM 1uM 0.5uM 0.25uM 0.125uM, and every kind of processing has four repetitions;
(3), after step 2 is handled 48h, detect with the activity of CCK-8 test kit pair cell: every hole adding 5ul CCK-8 solution, read the absorption value of each hole wavelength with microplate reader at the 450nm place; In cell culture incubator, continue to hatch 100min, read the absorption value of wavelength once more at the 450nm place with microplate reader; The changing value of getting twice absorption value changes divided by the absorption value that does not add the compound treatment hole, gets every group of four multiple mean values and is hole inner cell activity; The inhibition efficient of compound pair cell=1-hole inner cell activity will input to http://bsmdb.tmd.ac.jp:3000/cbdb/ic50 according to the gradient of compound concentration and cytoactive, calculate finally to obtain IC50.
6. the application of the described cantharidin derivative of claim 1～4 on synthesizing antineoplastic medicament.
CN201010197629A 2010-06-11 2010-06-11 Norcantharidin derivative and activity testing method and application thereof Pending CN101863909A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201010197629A CN101863909A (en) 2010-06-11 2010-06-11 Norcantharidin derivative and activity testing method and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201010197629A CN101863909A (en) 2010-06-11 2010-06-11 Norcantharidin derivative and activity testing method and application thereof

Publications (1)

Publication Number Publication Date
CN101863909A true CN101863909A (en) 2010-10-20

Family

ID=42955866

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201010197629A Pending CN101863909A (en) 2010-06-11 2010-06-11 Norcantharidin derivative and activity testing method and application thereof

Country Status (1)

Country Link
CN (1) CN101863909A (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111253415A (en) * 2020-03-17 2020-06-09 遵义医科大学 Norcantharidin carboxylic acid trifluorobenzyl ester and synthetic method and application thereof
CN111362962A (en) * 2020-03-17 2020-07-03 遵义医科大学 Tetrafluorobenzyl norcantharidin carboxylate and synthesis method thereof

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111253415A (en) * 2020-03-17 2020-06-09 遵义医科大学 Norcantharidin carboxylic acid trifluorobenzyl ester and synthetic method and application thereof
CN111362962A (en) * 2020-03-17 2020-07-03 遵义医科大学 Tetrafluorobenzyl norcantharidin carboxylate and synthesis method thereof
CN111253415B (en) * 2020-03-17 2022-08-09 遵义医科大学 Norcantharidin carboxylic acid trifluoro benzyl ester and synthetic method and application thereof

Similar Documents

Publication Publication Date Title
Hu et al. Synthesis and antiviral activity of coumarin derivatives against infectious hematopoietic necrosis virus
Zhang et al. Anti-Helicobacter pylori compounds from the ethanol extracts of Geranium wilfordii
Chang et al. The fractionated Toona sinensis leaf extract induces apoptosis of human ovarian cancer cells and inhibits tumor growth in a murine xenograft model
Ugale et al. Benzofurano-isatins: Search for antimicrobial agents
TW200732336A (en) Alyphactic heterocyclic compounds
CN101812066A (en) Pyrazolo N-substituted dehydronorcantharidin imide derivative as well as synthesis method, activity test method and application thereof
Peytam et al. Design and synthesis of new imidazo [1, 2-b] pyrazole derivatives, in vitro α-glucosidase inhibition, kinetic and docking studies
Fatima et al. Epicoccum sp., an emerging source of unique bioactive metabolites
Gupta et al. Alkaloids: a source of anticancer agents from nature
Gupta et al. Diversity and biological activity of fungal endophytes of Zingiber officinale Rosc. with emphasis on Aspergillus terreus as a biocontrol agent of its leaf spot
Abd El-Hameed et al. Synthesis of novel pyrroles and fused pyrroles as antifungal and antibacterial agents
Temiz-Arpaci et al. Synthesis and different biological activities of novel benzoxazoles
CN101863909A (en) Norcantharidin derivative and activity testing method and application thereof
Chabowska et al. Biological activity of naturally derived naphthyridines
CN106496203B (en) A kind of preparation method of quinolinones compound and the application as I type viral agent of anti-herpes simplex
Alaqeel et al. Antimicrobial activities of novel class of dispirooxindolopyrrolidine grafted indanedione hybrid heterocycles against carbapenemase producing Klebsiella pneumoniae (CKP)
Ibrahim et al. Synthesis, Characterization, and Antifungal Activity of Some New Thieno [2, 3-b] pyridines Incorporating Quinazoline or Benzimidazole Moiety
Reddy et al. New urea and thiourea derivatives of piperazine doped with febuxostat: synthesis and evaluation of anti-TMV and antimicrobial activities
CN101475532B (en) 1,5- diheterocyclic-1,4- pentadiene-3-keto derivative , and preparation and use thereof
Mor et al. Convenient synthesis of benzothiazinoisoindol-11-ones and benzoindenothiazin-11-ones, and antimicrobial testing thereof
CN102924429B (en) 1,2-naphthaquinone derivatives and preparation method thereof
Kovacic et al. New developments in the mechanism of drug action and toxicity of conjugated imines and iminiums, including related alkaloids
Hussain et al. Fruitful decade of Phoma secondary metabolites from 2011 to 2020: chemistry, chemical diversity, and biological activities
Kumar et al. Synthesis and Molecular Docking Studies of Some Pyrazole and Coumarin-based Hybrid Aurones as Antimicrobial Agents
CN103242348A (en) Indoline diketopiperazine spiro-compounds as well as preparation method and use thereof

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C12 Rejection of a patent application after its publication
RJ01 Rejection of invention patent application after publication

Application publication date: 20101020