CN106632043A - Licochalcone A pyrazoline derivatives with antitumor activity and synthesis method thereof - Google Patents
Licochalcone A pyrazoline derivatives with antitumor activity and synthesis method thereof Download PDFInfo
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- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
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Abstract
The invention relates to licochalcone A pyrazoline derivatives with antitumor activity and a synthesis method thereof. These compounds are synthesized by reacting licochalcone A and hydrazine compounds, which are adopted as raw materials, by adopting anhydrous alcohol as a solvent. The method is high in operation safety, mild in reaction condition and applicable to industrial production. Preliminary bioactivity tests show that these compounds have relatively high antitumor activity and important medical application value.
Description
Technical field
The present invention relates to medicinal chemistry arts, and in particular to a class has the licochalcone A pyrazoline of antitumor activity
Analog derivative and its synthetic method.
Background technology
Tumour is a kind of disease of serious threat human health, finds the little antineoplastic of effective and safe, toxic and side effect
The target that always tumour medicine R＆D worker seek assiduously.With pharmaceutical chemical development, with pyrazoline ring as structure
Effect of the compound of parent nucleus in oncotherapy causes extensive concern.
Pyrazoline ring is many native compounds and the core texture unit in synthetic drug, used as in heterocyclic compound
An important branch, pyrazoline class compound because its have efficiently, low toxicity, and its ring substituents can be with multi-faceted
Convert and be used widely in drug world.
The content of the invention
It is an object of the invention to provide a class tool antitumor activity licochalcone A pyrazoline analog derivative and its
Synthetic method.
The present invention's realizes that process is as follows：
General structure（I）Shown compound：
Wherein：R is hydrogen-based, and the alkyl of C1-C4, the alkoxyl of C1-C4, substituted or unsubstituted phenyl is substituted or unsubstituted
Benzyl, nitro；Described substituent is halogen, the alkoxyl of C1-C4, phenoxy group.
General structure（I）The synthetic method of shown compound, with licochalcone A and hydrazine class compound as raw material, to have
Machine alkali is reacted for catalyst；
。
Specifically comprise the steps of：
（1）It is in molar ratio 1 in reactor:1~1:1.5 add licochalcone A and hydrazine class compound, add organic solvent
It is well mixed, adds organic alkali catalyst, adjusts pH to 9-11,70 DEG C～85 DEG C back flow reactions 6～12 hours；
（2）By step（1）Column chromatographic isolation and purification after the solidliquid mixture reduced pressure concentration of reaction system, is dried to obtain target product
Thing.
Step（1）Described in the mol ratio of licochalcone A and hydrazine class compound be 1:1～1:1.3；Organic base catalytic
Agent is triethylamine；Organic solvent is absolute ethyl alcohol；Reaction temperature is 80 DEG C ~ 85 DEG C.
Research finds that pyrazoline class compound has anti-inflammatory, pain relieving, antibacterial, sterilized, antihyperglycemic, anticancer, anticoagulation
The pharmacologically actives such as agent, carboxyl is introduced into the chemical constitution of pyrazoline, is expected to strengthen its biologically active, improves selective, tool
There are important theory value and actual application value.
It is an advantage of the current invention that：Raw material environmental protection, low production cost, processing safety is high, and reaction condition is gentle, and reaction is former
Material is using abundant, it is adaptable to industrialized production, prior art low yield is solved the problems, such as, while pyridine ring is incorporated into Radix Glycyrrhizae
In the chemical constitution of chalcone A, the biologically active to probing into licochalcone A has important theoretical valency with structure-activity relationship is summarized
Value and using value.
Specific embodiment
With reference to specific embodiment, the present invention is further elaborated.These embodiments are only in order at the mesh of explanation
, and do not limit the scope of the invention and essence.
The licochalcone A pyrazoline analog derivative and its synthetic method of one class tool antitumor activity is specifically comprising as follows
Step：
（1）It is in molar ratio 1 in reactor:1~1:1.5 add licochalcone A and hydrazine class compound, plus absolute ethyl alcohol to mix
Close uniform, wherein solvent volume adds organic alkali catalyst triethylamine less than the 2/3 of reactor volume, adjusts pH to 9-11, is placed in
Stir on magnetic stirring apparatus, be heated to 70 DEG C～85 DEG C, back flow reaction 6～12 hours；
（2）Thin-layer chromatography is followed the trail of used in course of reaction, and what in time monitoring was reacted carries out degree, is stopped after raw material reaction is complete
Heating, removes condensing unit；
（3）By step（2）Column chromatographic isolation and purification after the solidliquid mixture reduced pressure concentration of reaction system, is dried to obtain target product
Thing.
Structural formula of compound in certain preferred embodiments of the present invention is as follows：
Embodiment 1
4-（3-（4- hydroxy phenyls）-1-（P-methylphenyl）- 4,5- dihydro -1H- pyrazoline -5- bases）- 5- methoxyl group -2-（2-
Methyl butyl- 3- alkene -2- bases）Phenol（1）Preparation.
200mg (1mmol) licochalcone As and 93.87mg (1.3mmol) are added in the reactor to procarbazine, plus
50ml absolute ethyl alcohols make reaction dissolvent, plus 0.5mL triethylamines as catalyst, are placed on magnetic stirring apparatus and stir, and use electric jacket
75 DEG C are heated to, back flow reaction 10 hours.Thin-layer chromatography following response, after reaction terminates, the solid-liquid of above-mentioned reaction system is mixed
After compound reduced pressure concentration, column chromatography for separation purification is crossed, be dried to obtain brown crystalline powder（135mg）, total recovery 51.61%.
Brown color crystalline powder solid.1H NMR (400MHz, DMSO-d6, 300K):d 7.85 (2H, d, J=
7.52Hz), 7.01(2H,d, J=7.52Hz), 6.95 (1H, s), 6.85 (2H, d, J=8.02Hz), 6.48
(2H, d, J=8.02Hz), 6.41(1H,s), 6.30(1H,q), 5,35(2H,s), 5.19 (1H, t), 5.00-
4.98 (2H, m), 3.90-3,65 (2H, m), 3.83 (3H, s), 2.34 (3H, s), 1.69 (6H,s).13C
NMR (75MHz, DMSO-d6) δ (ppm): 160.8, 155.1, 154.7, 151.7, 148.8, 140.8,
129.3, 128.3, 125.2, 121.6, 116.0, 113.4, 111.1, 103.8, 56.1, 54.8, 40.3,
39.8, 28.6, 21.3. HRMS (ESI) for (M+H)+: calcd: 443.23, found:443.78。
Embodiment 2
4-（3-（4- hydroxy phenyls）-1-（4- methoxyphenyls）- 4,5- dihydro -1H- pyrazoline -5- bases）- 5- methoxyl group -2-
（2- methyl butyl- 3- alkene -2- bases）Phenol（2）Preparation.
200mg (1mmol) licochalcone As and 106.16mg (1.3mmol) are added in the reactor to methoxyl group phenylhydrazine,
Plus 50ml absolute ethyl alcohols make reaction dissolvent, plus 0.5mL triethylamines as catalyst, it is placed on magnetic stirring apparatus and stirs, uses electric heating
Set is heated to 80 DEG C, back flow reaction 6 hours.Thin-layer chromatography following response, after reaction terminates, the solid-liquid of above-mentioned reaction system is mixed
After compound reduced pressure concentration, column chromatography for separation purification is crossed, be dried to obtain brown crystalline powder（127mg）, total recovery 46.86%.
Brown crystalline powder solid.1H NMR (400MHz, DMSO-d6, 300K): d 7.85 (2H, d, J=
7.52Hz), 6.95 (1H, s), 6.85 (2H, d, J=7.52Hz), 6.77 (2H, d, J=7.43Hz), 6.49
(2H, d, J=7.43Hz), 6.41 (1H, s), 6.30 (1H, q), 5.35 (2H, s), 5.19 (1H, t),
5.00-4.98 (2H, m), 3.90-3.65 (2H, m), 3.83 (6H, s), 1.69 (6H, s). 13C NMR
(75MHz, DMSO-d6) δ (ppm): 160.8, 155.1, 154.7, 151.7, 148.8, 136.1, 129.1,
128.3, 125,2, 121.6, 116.0, 115.1, 114.5, 111.1, 103.8, 56.1, 55.8, 54.8,
40.3, 39.8, 28.6.HRMS (ESI) for (M+H)+: calcd: 459.22, found:459.55。
Embodiment 3
4-（1-（4- fluorophenyls）-3-（4- hydroxy phenyls）- 4,5- dihydro -1H- pyrazoline -5- bases）- 5- methoxyl group -2-（2-
Methyl butyl- 3- alkene -2- bases）Phenol（3）Preparation.
200mg (1mmol) licochalcone As and 96.91mg (1.3mmol) are added in the reactor（4- fluorophenyls）Hydrazine,
Plus 50ml absolute ethyl alcohols make reaction dissolvent, plus 0.5mL triethylamines as catalyst, it is placed on magnetic stirring apparatus and stirs, uses electric heating
Set is heated to 80 DEG C, back flow reaction 8 hours.Thin-layer chromatography following response, after reaction terminates, the solid-liquid of above-mentioned reaction system is mixed
Column chromatography for separation purification is crossed after compound reduced pressure concentration, brown crystalline powder is dried to obtain（114.2mg）, total recovery 43.27%.
Brown crystalline powder solid.1H NMR (400MHz, DMSO-d6, 300K): d 7.85 (2H, d, J=
7.52Hz), 7.02 (2H, d, J=7.52Hz ), 6.95 (1H, s), 6.85 (2H, d, J=7.43Hz), 6.58
(2H, d,J=7.43Hz), 6.41 (1H, s), 6.30 (1H, q), 5.35 (2H, s), 5.19 (1H, t),
5.00-4.98 (2H, m), 3.90-3.65 (2H, m), 3.83 (6H, s), 1.69 (6H, s). 13C NMR
(75MHz, DMSO-d6) δ (ppm): 160.8, 155.7, 155.1, 154.7,151.7, 148.8, 139.4,
129.1, 128.3, 125,2, 121.6, 116.2,115.1, 111.1, 103.8, 56.1, 54.8, 40.3,
39.8, 28.6. HRMS(ESI)for(M+H)+: calcd:447.20, found:447.55。
Embodiment 4
4-（3-（4- hydroxy phenyls）-1-（4- nitrobenzophenones）- 4,5- dihydro -1H- pyrazoline -5- bases）- 5- methoxyl group -2-
（2- methyl butyl- 3- alkene -2- bases）Phenol（4）Preparation.
200mg (1mmol) licochalcone As and 117.66mg (1.3mmol) paranitrophenylhydrazine are added in the reactor,
Plus 50ml absolute ethyl alcohols make reaction dissolvent, it is placed on magnetic stirring apparatus and stirs, with electric jacket 85 DEG C are heated to, back flow reaction 10 is little
When.Thin-layer chromatography following response, after reaction terminates, by the solidliquid mixture reduced pressure concentration of above-mentioned reaction system after, add water, plus first
Alcohol, it is cold to put crystallization.After crystallization, filter, filtrate crosses column chromatography, column chromatography for separation purification is dried to obtain brown crystalline powder
（142.25mg）, total recovery 50.83%.
Brown crystalline powder solid.1H NMR (400MHz, DMSO-d6, 300K): d 8.64 (2H, d, J=
7.32Hz), 7.85 (2H, d, J=7.32Hz), 7.17 (2H, d, J=7.53Hz), 6.95 (1H, s), 6.85
(2H, d, J=7.53Hz), 6.41 (1H, s), 6.30 (1H, q), 5.35 (2H, s), 5.19 (1H, t),
5.00-4.98 (2H, m), 3.90-3.65 (2H, m), 3.83 (6H, s), 1.69 (6H, s). 13C NMR
(75MHz, DMSO-d6) δ (ppm): 160.8, 155.1, 154.7, 151.7, 149.9, 148.8, 136.3,
129.1, 128.3, 125,2, 124.7, 121.6, 116.0, 111.2, 103.8, 56.1, 54.8, 40.3,
39.8, 28.6. HRMS (ESI) for (M+H) +:calcd:474.20, found:474.55。
Embodiment 5
4-（1-（4- chlorphenyls）-3-（4- hydroxy phenyls）- 4,5- dihydro -1H- pyrazoline -5- bases）- 5- methoxyl group -2-（2-
Methyl butyl- 3- alkene -2- bases）Phenol（5）Preparation.
200mg (1mmol) licochalcone As and 109.55mg (1.3mmol) are added in the reactor（4- chlorphenyls）
Hydrazine, plus 50ml absolute ethyl alcohols make reaction dissolvent, plus 0.5mL triethylamines as catalyst, are placed on magnetic stirring apparatus and stir, electricity consumption
Hot jacket is heated to 80 DEG C, back flow reaction 12 hours.Thin-layer chromatography following response, after reaction terminates, by consolidating for above-mentioned reaction system
After liquid mixture reduced pressure concentration, column chromatography for separation purification is crossed, be dried to obtain brown crystalline powder（113.6mg）, total recovery
41.52%。
Brown crystalline powder solid.1H NMR (400MHz, DMSO-d6, 300K): d 7.85 (2H, d, J=
7.52Hz), 7.27 (2H, d,J=7.52Hz), 6.95 (1H, s),6.85 (2H, d, J=7,43Hz), 6.54
(2H, d, J=7.43Hz), 6.41 (1H, s), 6.30 (1H ,q), 5.35 (2H, s), 5.19 (1H, t),
5.00-4.98 (2H, m), 3.90-3.65 (2H, m), 3.83 (6H, s), 1.69 (6H, s). 13C NMR
(75MHz, DMSO-d6) δ (ppm): 160.8, 155.1, 154.7, 151.7, 148.8, 141.9, 129.2,
128.3, 125.2, 121.6, 116.0, 114.9, 111.1, 103.8, 56.1, 54.8, 40.3, 39.8,
28.6. HRMS (ESI) for (M+H) +:calcd: 463.17, found:463.55。
Embodiment 6
4-（1-（4- bromophenyls）-3-（4- hydroxy phenyls）- 4,5- dihydro -1H- pyrazoline -5- bases）- 5- methoxyl group -2-（2-
Methyl butyl- 3- alkene -2- bases）Phenol（6）Preparation.
200mg (1mmol) licochalcone As and 143.71mg (1.3mmol) are added in the reactor（4- bromophenyls）
Hydrazine, plus 50ml absolute ethyl alcohols make reaction dissolvent, plus 0.5mL triethylamines as catalyst, are placed on magnetic stirring apparatus and stir, electricity consumption
Hot jacket is heated to 80 DEG C, back flow reaction 10 hours.Thin-layer chromatography following response, after reaction terminates, by consolidating for above-mentioned reaction system
Column chromatography for separation purification is crossed after liquid mixture reduced pressure concentration, brown crystalline powder is dried to obtain（148.23mg）, total recovery
49.43%。
Brown crystalline powder solid.1H NMR (400 MHz,DMSO-d6, 300K)：d7.85 (2H,d), 7.38
(2H,d), 6.95 (1H,s), 6.85 (2H,d),6.49 (2H,d), 6.41 (1H,s), 6.30 (1H, q, J=
7.6,7.5HZ), 5.35 (2H,s), 5.19 (1H,t), 4.98-5.00 (2H,m), 3.65-3.90 (5H,m),
1.69(6H,s). 13CNMR (75MHz, DMSO-d6) δ (ppm): 160.8, 155.1, 151.7, 148.8,
142.8, 132.4, 129.1, 129.0, 128.3, 125.2, 121.6, 116.0, 115.1, 113.4, 111.1,
103.4, 56.1, 54.8, 40.3, 39.8, 28.6. HRMS (ESI) for (M+H)+: calcd: 507.1205,
found:507.1311。
Embodiment 7
4-（3-（4- hydroxy phenyls）-1-（3- nitrobenzophenones）- 4,5- dihydro -1H- pyrazoline -5- bases）- 5- methoxyl group -2-
（2- methyl butyl- 3- alkene -2- bases）Phenol（7）Preparation.
200mg (1mmol) licochalcone As and 117.66mg (1.3mmol) m-nitro phenylhydrazine are added in the reactor,
Plus 50ml absolute ethyl alcohols make reaction dissolvent, plus 0.5mL triethylamines as catalyst, it is placed on magnetic stirring apparatus and stirs, uses electric heating
Set is heated to 70 DEG C, back flow reaction 10 hours.Thin-layer chromatography following response, after reaction terminates, by the solid-liquid of above-mentioned reaction system
After mixture reduced pressure concentration, column chromatography for separation purification is crossed, be dried to obtain brown crystalline powder（115.8mg）, total recovery
41.38%。
Brown crystalline powder solid.1H NMR (400 MHz,DMSO-d6, 300K)：d7.85 (2H,d), 7.49-
7.64 (4H,m), 6.95(1H,s), 6.85(2H,d), 6.41(1H,s), 6.30 (1H,q,J=7.4,7.3Hz),
5.35 (2H,s), 5.19 (1H,t), 5.00 (2H,m), 3.65-3.90 (5H,m), 1.69 (6H,s). 13CNMR
(75MHz, DMSO-d6) δ (ppm): 160.8, 155.1, 154.7, 151.7, 148.8, 144.7, 130.4,
129.1, 128.3, 125.2, 122.8, 121.6, 116.0, 112.3, 111.1, 106.4, 103.8, 56.1,
54.8, 40.3, 39.8, 28.6. HRMS (ESI) for (M+H)+: calcd: 474.1951, found：
474.2004。
Embodiment 8
4-（3-（4- hydroxy phenyls）- 4,5- dihydro -1H- pyrazoline -5- bases）- 5- methoxyl group -2-（2- methyl butyl- 3- alkene -2-
Base）Phenol（8）Preparation.
200mg (1mmol) licochalcone As and 24.62mg (1.3mmol) hydrazine hydrate, plus 50ml are added in the reactor
Absolute ethyl alcohol makees reaction dissolvent, plus 0.5mL triethylamines as catalyst, is placed on magnetic stirring apparatus and stirs, and is heated with electric jacket
To 80 DEG C, back flow reaction 10 hours.Thin-layer chromatography following response, after reaction terminates, by the solidliquid mixture of above-mentioned reaction system
After reduced pressure concentration, column chromatography for separation purification is crossed, be dried to obtain brown crystalline powder（115.1mg）, total recovery 55.26%.
Brown crystalline powder solid.1H NMR (400 MHz,DMSO-d6, 300K)：d7.85(2H,d),7.0(1H,
d), 6.95(1H,s), 6.85 (2H,d), 6.41 (1H,s), 6.30 (1H, q, J=7.6, 7.5Hz), 5.35
(2H, s), 4.98-5.00 (2H,m), 3.69-3.9 (3H, m), 3.83 (3H, s), 1.69 (6H,s). 13CNMR
(75MHz, DMSO-d6) δ (ppm): 160.8, 155.1, 154.7, 151.7, 148.8, 129.1, 129.0,
128.3, 125.2, 121.6, 116.0, 111.1, 103.8, 56.1, 45.5, 42.9, 39.8, 28.6. HRMS
(ESI) for (M+H)+: calcd:353.1787,found:353.1974。
Embodiment 9
4-（3-（4- hydroxy phenyls）- 1- methyl -4,5- dihydro -1H- pyrazoline -5- bases）- 5- methoxyl group -2-（2- methyl butyl-
3- alkene -2- bases）Phenol（9）Preparation.
200mg (1mmol) licochalcone As and 35.4mg (1.3mmol) methyl hydrazine, plus 50ml are added in the reactor
Absolute ethyl alcohol makees reaction dissolvent, plus 0.5mL triethylamines as catalyst, is placed on magnetic stirring apparatus and stirs, and is heated with electric jacket
To 80 DEG C, back flow reaction 10 hours.Thin-layer chromatography following response, after reaction terminates, by the solidliquid mixture of above-mentioned reaction system
After reduced pressure concentration, column chromatography for separation purification is crossed, be dried to obtain brown crystalline powder（99.7mg）, total recovery 46.03%.
Brown crystalline powder solid.1H NMR (400 MHz, DMSO-d6, 300K)：d 7.85 (2H, d),
6.95 (1H, s), 6.85 (2H, d), 6.41 (1H, s), 6.30 (1H, t), 5.35 (1H, s), 5.00
(1H, s), 4.98 (1H, s), 3.7 (1H, t), 3.83 - 3.54 (5H, m), 3.00 (3H, s), 1.69
(6H, s). 13C NMR (75MHz, DMSO-d6 ) δ (ppm): 160.8, 156.1, 155.0, 151.7, 148.8,
129.3, 129.1, 129.0, 125.2, 116.4, 116.0, 111.1, 103.8, 56.1, 54.9, 41.1,
40.4, 39.8, 28.6. HRMS (ESI) for (M+H)+: calcd:367.1943, found: 367.1978。
Embodiment 10
4-（1-（The tert-butyl group）-3-（4- hydroxy phenyls）- 4,5- dihydro -1H- pyrazoline -5- bases）- 5- methoxyl group -2-（2- first
Base butyl- 3- alkene -2- bases）Phenol（10）Preparation.
200mg (1mmol) licochalcone As and 67.73mg (1.3mmol) tertiary butyl hydrazine are added in the reactor, plus
50ml absolute ethyl alcohols make reaction dissolvent, plus 0.5mL triethylamines as catalyst, are placed on magnetic stirring apparatus and stir, and use electric jacket
80 DEG C are heated to, back flow reaction 10 hours.Thin-layer chromatography following response, after reaction terminates, the solid-liquid of above-mentioned reaction system is mixed
After compound reduced pressure concentration, column chromatography for separation purification is crossed, be dried to obtain brown crystalline powder（98.2mg）, total recovery 40.67%.
Brown crystalline powder solid.1H NMR (400 MHz, DMSO-d6, 300K)：d 7.85 (2H, d),
6.95 (1H, s), 6.85 (2H, d), 6.41 (1H, s), 6.3 (1H, t), 5.35 (1H, s), 5.00
(1H, s), 4.98 (1H, s), 3.9 (1H, t), 3.83-3.54 (5H, m), 1.69 (6H, s), 1.27
(9H, s). 13C NMR (75MHz, DMSO-d6) δ (ppm): 160.8, 156.1, 155.0, 151.7, 148.8,
129.3, 129.1, 129.0, 125.2, 116.4, 116.0, 111.1, 103.8, 74.6, 56.1, 47.4,
41.3, 39.8, 28.6. HRMS (ESI) for (M+H)+: calcd:409.2413, found: 409.2487。
Embodiment 11
The antitumor activity test of the compounds of this invention
Cytostatic to tumor cell test is carried out to the compound of the present invention, test method is using conventional mtt assay.
Cell line is selected：Human liver cancer cell (HepG2), human lung carcinoma cell (A-549), human cervical carcinoma cell (Hela), human gastric cancer
Cell (SGC-7901), human colon cancer cell (HCT-8).Nutrient solution is that DMEM+15%NBS+ is dual anti-.
The preparation of sample liquid：After with DMSO (Merck) dissolvings, add the solution of 100 μm of ol/L that PBS (-) is made into or
Uniform suspension, then with PBS (-) dilution of DMSO, ultimate density is respectively 0.1,1,10,20,40,60,80,100 μ
mol/L。
The antineoplastic cytarabine (Ara-C) of listing is made into reference substance solution with same condition.
Cell culture：Adherent growth tumor cell is incubated at containing 10% inactivation NBCS and penicillin, strepto-
Element（Each 1,000,000 U/L）RPMI-1640 in, be placed in 37 DEG C, 5% CO2, cultivate in the CO2gas incubator of saturated humidity.
Cell attachment grows, and passes on per 2～3 days 1 time, pours out nutrient solution when passing on first, and PBS is washed 2 times, after pancreatin digestion, adds
Fresh nutrient solution piping and druming is uniform, adjusts cell to debita spissitudo and moves into new blake bottle, and addition nutrient solution is to appropriate.It is right to take
Number growth period cell is used to test.
Mtt assay detects cytoactive and IC50Measure：
Experimental principle：The MTT of yellow can be reduced into water-fast bluish violet Chan Wu formazans by dehydrogenase in living cells mitochondria
(MTT formazan), and be deposited in cell, the amount of generation is directly proportional to number of viable cells, and dead cell does not have this work(
Energy.DMSO can dissolve bluish violet crystal, and shade is directly proportional to contained amount, therefore the absorbance value determined with ELIASA
Cell survival rate can be reflected.
Experimental technique：Take the logarithm growth period cell, digestion, count, 96 holes are inoculated in the density of 2 × 104/mL
In culture plate, per the μ l of hole 100.After culture 24 hours, by testing compound with 0.1,1,10,20,40,60,80,100 μ
Mol/L concentration processes cell.Experimental group each concentration sets 5 multiple holes, is compared with the nutrient solution containing 0.4% DMSO.Medicine is made
After with 48 hours, supernatant is removed, 100 μ l MTT are added per hole（2- (4,5- dimethyl -2- thiazolyls) -3,5- diphenyl -2H-
Tetrazolium hydrobromate）(1mg/mL), continue to cultivate 4 hours, abandon supernatant, add 100 μ l DMSO, vibration to mix per hole, use enzyme
Mark instrument mensuration absorbance value at 570 nm, using IC50Software for calculation obtains half-inhibition concentration (IC50).
Result of the test refers to table 1, wherein, sample refers to that the licochalcone A pyridines prepared in corresponding embodiment derive
Thing, sample number into spectrum correspondence prepares the concrete numbering of compound resulting in embodiment.
Compound 8 shows good antitumor activity, compound 2,7 and 9 times in the 5 kinds of cell lines tested
It, also shows good antitumor activity in different cell lines.Above test result indicate that, the present invention compound
With good antitumor activity, particularly the activity of part licochalcone A pyrazoline class compound is in specific cells strain
Middle antitumor activity is better than or is equal to cytarabine.
Half-inhibition concentration IC of the compound of table 1 to different tumour cells50（Unit：μmol/L）
Claims (7)
1. general structure（I）Shown compound：
Wherein：R is hydrogen, nitro, the alkyl of C1-C4, the alkoxyl of C1-C4, substituted or unsubstituted phenyl, replacement or unsubstituted
Benzyl；Described substituent is halogen, the alkoxyl of C1-C4, phenoxy group.
2. general structure（I）The synthetic method of shown compound, it is characterised in that：It is by licochalcone A and hydrazine class compound
Raw material, is reacted by catalyst of organic base,
。
3. synthetic method according to claim 2, it is characterised in that comprise the steps of：
（1）It is in molar ratio 1 in reactor:1~1:1.5 add licochalcone A and hydrazine class compound, add absolute ethyl alcohol
It is well mixed, adds organic alkali catalyst triethylamine, adjusts pH to 9-11,70 DEG C～85 DEG C back flow reactions 6～12 hours；
（2）By step（1）Column chromatographic isolation and purification after the solidliquid mixture reduced pressure concentration of reaction system, is dried to obtain target product
Thing.
4. synthetic method according to claim 3, it is characterised in that：Step（1）Described in licochalcone A and hydrazine
The mol ratio of compound is 1:1～1:1.3.
5. synthetic method according to claim 3, it is characterised in that：Step（1）Middle reaction temperature is 80 DEG C ~ 85 DEG C.
6. application of the compound described in claim 1 in treatment antineoplastic is prepared.
7. apply according to claim 6, it is characterised in that described tumour is liver cancer, lung cancer, cervical carcinoma, cancer of the stomach, colon
Cancer.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107235915A (en) * | 2017-02-24 | 2017-10-10 | 陕西科技大学 | A kind of licochalcone A with antitumor activity and buformin cyclized derivative and its synthetic method |
| CN107311953A (en) * | 2016-12-31 | 2017-11-03 | 陕西科技大学 | A kind of dihydro-isoxazole licochalcone A and its synthetic method for having antitumor activity |
| CN107311936A (en) * | 2017-02-24 | 2017-11-03 | 陕西科技大学 | A kind of licochalcone A with antitumor activity and insoral cyclized derivative and its synthetic method |
| CN107445903A (en) * | 2017-02-24 | 2017-12-08 | 陕西科技大学 | A kind of licochalcone A with antitumor activity and melbine cyclized derivative and its synthetic method |
| CN110128342A (en) * | 2019-05-05 | 2019-08-16 | 天津科技大学 | The pyrazoline analog derivative and synthetic method and application that a kind of 3,5- diphenyl with anti-tumor activity replaces |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104961735A (en) * | 2015-07-20 | 2015-10-07 | 武汉理工大学 | Pyrazoline derivative and application of pyrazoline derivative as tyrosinase inhibitor |
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2016
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107311953A (en) * | 2016-12-31 | 2017-11-03 | 陕西科技大学 | A kind of dihydro-isoxazole licochalcone A and its synthetic method for having antitumor activity |
| CN107235915A (en) * | 2017-02-24 | 2017-10-10 | 陕西科技大学 | A kind of licochalcone A with antitumor activity and buformin cyclized derivative and its synthetic method |
| CN107311936A (en) * | 2017-02-24 | 2017-11-03 | 陕西科技大学 | A kind of licochalcone A with antitumor activity and insoral cyclized derivative and its synthetic method |
| CN107445903A (en) * | 2017-02-24 | 2017-12-08 | 陕西科技大学 | A kind of licochalcone A with antitumor activity and melbine cyclized derivative and its synthetic method |
| CN110128342A (en) * | 2019-05-05 | 2019-08-16 | 天津科技大学 | The pyrazoline analog derivative and synthetic method and application that a kind of 3,5- diphenyl with anti-tumor activity replaces |
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