CN105859777B - Suppress aloe-emodin quaternary alkylphosphonium salt of group and preparation method thereof containing glycolysis - Google Patents

Suppress aloe-emodin quaternary alkylphosphonium salt of group and preparation method thereof containing glycolysis Download PDF

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CN105859777B
CN105859777B CN201610303228.7A CN201610303228A CN105859777B CN 105859777 B CN105859777 B CN 105859777B CN 201610303228 A CN201610303228 A CN 201610303228A CN 105859777 B CN105859777 B CN 105859777B
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aloe
emodin
quaternary alkylphosphonium
alkylphosphonium salt
emodin quaternary
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CN105859777A (en
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邵敬伟
范露露
李晓
杨祥
李诗琪
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Fuzhou University
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    • C07ORGANIC CHEMISTRY
    • C07FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02Phosphorus compounds
    • C07F9/28Phosphorus compounds with one or more P—C bonds
    • C07F9/54Quaternary phosphonium compounds
    • C07F9/5456Arylalkanephosphonium compounds

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Abstract

The invention discloses a kind of aloe-emodin quaternary alkylphosphonium salt dichloroacetic acid ester for suppressing group containing glycolysis and preparation method thereof;Aloe-emodin first reacts to obtain bromo aloe-emodin with phosphorus tribromide, and octyl group reacts generation aloe-emodin quaternary alkylphosphonium salt with tri-n-octyl phosphine again, and esterification finally, which occurs, with dichloroacetyl chloride obtains aloe-emodin quaternary alkylphosphonium salt dichloroacetic acid ester:.The cancer cell in vitro of aloe-emodin quaternary alkylphosphonium salt dichloroacetic acid ester suppresses experiment and shows there is inhibitory activity to a variety of cancer cells, has larger application prospect in terms of antineoplastic is prepared.

Description

Suppress aloe-emodin quaternary alkylphosphonium salt of group and preparation method thereof containing glycolysis
Technical field
The invention belongs to the preparation field of cancer therapy drug, and in particular to a kind of aloe rheum officinale for suppressing group containing glycolysis Su quaternary alkylphosphonium salt dichloroacetic acid esters and preparation method thereof.
Background technology
Cancer cell is with " Warburg effect ", i.e. cancer cell still tend to sugar under conditions of oxygen supply is sufficient Glycolysis, thus by suppress cancer cell glycolysis suppress tumor cell viability be current pharmaceutical chemistry circle generally acknowledge it is extremely important Anti-Cancer Drug Design thinking.Physician generally studies medicine by the way of chemotherapeutic and glycolytic inhibitor drug combination at present Anticancer mechanism.
Aloe-emodin(AE)It for the antibiotic effective ingredient of rheum officinale, can be extracted from aloe, there is antitumor activity, antibacterial Activity and immunosuppressive action isoreactivity.But the activity of aloe-emodin in itself is weaker, and therefore, aloe-emodin is tied Structure modification improves its activity, has great application prospect.This seminar earlier studies have shown that, aloe-emodin quaternary alkylphosphonium salt(AP) With good active anticancer.It can be pressed down with glycolytic inhibitor 2-DG combinations by reducing the mitochondrial membrane potential of cancer cell Cancer cell mitochondrial function processed, strengthen the active anticancer of rheum emodin quaternary alkylphosphonium salt.But found during drug combination, 2-DG Dosage it is bigger than normal, be also easy to produce toxic side effect;Drug combination is difficult to ensure that medicine while reaches cancer location simultaneously, it is also difficult to Ensure that medicine can produce Synergistic anti-cancer effect with suitable concentration.
Dichloroacetic acid(DCA)It is famous glycolytic inhibitor, pyruvic dehydrogenase kinase activity can be activated, make pyruvic acid It is converted into acetylcoenzyme and enters aerobic metabolism approach, so as to suppresses anaerobic metabolism approach (i.e. glycolytic pathway).The present invention will be big Flavine quaternary alkylphosphonium salt is coupled with dichloroacetic acid by esterification, forms aloe-emodin quaternary alkylphosphonium salt dichloroacetic acid ester(AP- DCA).On the one hand strengthen the active anticancer of aloe-emodin quaternary alkylphosphonium salt;On the other hand the dosage of glycolytic inhibitor is made Reduce, reduce toxic side effect.
The content of the invention
It is an object of the invention to provide a kind of aloe-emodin quaternary alkylphosphonium salt dichloroacetic acid for suppressing group containing glycolysis Ester and preparation method thereof.It is used as lipophilic cation targetted mitochondria by introducing long carbochain quaternary alkylphosphonium salt on aloe-emodin, A dichloroacetic acid ester is re-introduced into, to produce dichloroacetic acid after hydrolyzing as glycolytic inhibitor, so as to greatly improve aloe The active anticancer of rheum emodin.
To achieve the above object, the present invention adopts the following technical scheme that:
A kind of aloe-emodin quaternary alkylphosphonium salt dichloroacetic acid ester for suppressing group containing glycolysis, its structural formula are as follows:
The preparation method of described aloe-emodin quaternary alkylphosphonium salt dichloroacetic acid ester, is concretely comprised the following steps:
1)The synthesis of bromo aloe-emodin:3.70 mmol aloe-emodins are dissolved in 100 mLCCl4In, add at room temperature Enter 10.8 mmol PBr3, 65 DEG C are warming up to, stirred at reflux reacts 24 h;Revolving removes solvent, and residue is through silica gel column layer Analysis purifying, obtains bromo aloe-emodin;
2)The synthesis of aloe-emodin quaternary alkylphosphonium salt:1.00 mmol bromo aloe-emodins are dissolved in 15 mL acetone, room temperature 1.12 mmol tri-n-octyl phosphines of lower addition, are warming up to 50 DEG C, react 6 h, and solvent is spin-dried for by reaction after terminating, and uses dichloromethane Wet method loading, aloe-emodin quaternary alkylphosphonium salt is obtained through silica gel column chromatography gradient elution;
3)The synthesis of aloe-emodin quaternary alkylphosphonium salt dichloroacetic acid ester:By 0.14 mmol aloe-emodins quaternary alkylphosphonium salt and 1.09 Mmol potassium carbonate is dissolved in there-necked flask with 20 mL acetone, is warming up to 37 DEG C of 0.5 h of stirring, is added 1.05 mmol dichloroacetyls Chlorine, the h of stirring reaction 3;Stop removing solvent with Rotary Evaporators after reacting, with dichloromethane wet method loading, gradient elution is carried out Column chromatography purifies, and obtains aloe-emodin quaternary alkylphosphonium salt dichloroacetic acid ester.
Step 1)Middle silica gel column chromatography purifying eluant, eluent used is CH2Cl2
Step 2)The order of middle gradient elution is:V(CH2Cl2):V(C2H5OH)= 40:1→30:1→25:1→20:1。
Step 3)The eluting order of middle gradient elution is:V(CH2Cl2):V(C2H5OH)=40:1→30:1→25:1→20: 1。
A kind of aloe-emodin quaternary alkylphosphonium salt dichloroacetic acid ester for suppressing group containing glycolysis as described above is controlled in preparation Treat the application in cancer drug;Described cancer includes lung cancer and liver cancer.
The remarkable advantage of the present invention is:
Glycolytic inhibitor is introduced aloe-emodin quaternary alkylphosphonium salt by the present invention by the method for chemical bonding, utilizes cancer cell The high feature of hydrolytic enzyme activities, it is ensured that chemotherapeutic aloe-emodin quaternary alkylphosphonium salt can arrive simultaneously with glycolytic inhibitor dichloroacetic acid Up to cancer cell position and produce Synergistic anti-cancer effect;Active anticancer test shows that the medicine has preferable active anticancer, and it is to more Kind cancer cell has inhibited proliferation, and it is broad-spectrum anti-cancer drug to be expected to exploitation.
Brief description of the drawings
The synthetic route of Fig. 1 aloe-emodin quaternary alkylphosphonium salt dichloroacetic acid esters;
Inhibitory activity (the IC to lung cell A549 such as Fig. 2 dichloroacetic acid and aloe-emodin and its derivative50, μ M);
Inhibitory activity (the IC to hepatocellular carcinoma H22 such as Fig. 3 dichloroacetic acid and aloe-emodin and its derivative50, μ M)。
Embodiment
In order that content of the present invention easily facilitates understanding, with reference to embodiment to of the present invention Technical scheme is described further, but the present invention is not limited only to this.
Embodiment 1
A kind of preparation method of aloe-emodin quaternary alkylphosphonium salt dichloroacetic acid ester, is concretely comprised the following steps:
1)The synthesis of bromo aloe-emodin
The mmol of aloe-emodin 3.70 is dissolved in 100 mLCCl4In, 10.8 mmol PBr are added at room temperature3, it is warming up to 65 DEG C, stirred at reflux reacts 24 h;After revolving removes solvent, residue purifies through silica gel column chromatography(Eluant, eluent CH2Cl2) Obtain orange/yellow solid bromo aloe-emodin;Characterization of The Products data are as follows:
Yield 72.1%;m.p. 72-73℃;Rf(CH2Cl2)=0.74; 1H NMR (400 MHz, CDCl3) δ: 12.09 (s, 1H, ArOH), 12.06 (s, 1H, ArOH), 7.89 (d, J=5.2 Hz, 1H, ArH), 7.88 (s, 1H, ArH), 7.73 (t, J=7.6 Hz, 1H, ArH), 7.36 (s, 1H, ArH), 7.35 (d, J=6.4 Hz, 1H, ArH), 4.51 (s, 2H, ArCH2Br); ESI-MS m/z 331.1 (M-H)-; HRMS m/z 330.9619 theoretical value (M-H)- 330.9611.
2)The synthesis of aloe-emodin quaternary alkylphosphonium salt
By step 1)The mmol of bromo aloe-emodin 1.00 of synthesis is dissolved in 15 mL acetone, adds 1.12 at room temperature Mmol tri-n-octyl phosphines, 50 DEG C are warming up to, react 6 h, solvent is spin-dried for by reaction after terminating, with dichloromethane wet method loading, warp Silica gel column chromatography gradient elution obtains aloe-emodin quaternary alkylphosphonium salt;Characterize data is as follows:
Yield 51.2%;m.p. 54-56℃;Rf(CH2Cl2:C2H5OH=20:1) = 0.21;1H NMR (400 MHz, CDCl3) δ: 11.75 (br, 2H, OH), 7.63 (t, J=7.6Hz, 1H, Ar-H), 7.58 (m, 1H, Ar- H), 7.57 (m, 2H, Ar-H), 7.17 (m, 1H, Ar-H), 4.67 [s, 1H, ArCH 2P+(C8H17)3], 4.63 [s, 1H, ArCH 2P+(C8H17)3], 2.38 (m, 6H, P+(CH 2C7H15)3), 1.49-1.21 [m, 36H, 3×CH2 (C6 H 12CH3)3], 0.81 (t, 9H, CH3); 13C NMR (400 MHz, CDCl3) δ: 192.1, 180.4, 162.7, 162.5, 140.5, 137.4, 133.8, 132.9, 126.0, 124.9, 120.7, 120.1, 115.3, 115.1, 31.7, 31.6, 31.2, 31.1, 30.8, 30.7, 29.0, 28.9, 28.8, 22.6, 22.5, 21.9, 21.6, 19.5, 19.0, 14.0; LC-MS( ESI) m/z: 623.67(M-Br)+.
3)The synthesis of aloe-emodin quaternary alkylphosphonium salt dichloroacetic acid ester
By step 2)The mmol of aloe-emodin quaternary alkylphosphonium salt 0.14 of synthesis and 1.09 mmol potassium carbonate are molten with 20 mL acetone In there-necked flask, 37 DEG C of 0.5 h of stirring are warming up to, add 1.05 mmol dichloroacetyl chlorides, the h of stirring reaction 3;Stop reaction Solvent is removed with Rotary Evaporators afterwards, with dichloromethane wet method loading, gradient elution carries out column chromatography purification, obtains rufous and glue Thick solid, i.e. aloe-emodin quaternary alkylphosphonium salt dichloroacetic acid ester;Characterization of The Products data are:
Yield 36.6%;m.p. 46-48℃;Rf(CH2Cl2:C2H5OH=20:1) = 0.20; 1H NMR (400 MHz, CDCl3) δ: 7.70 (d, J=7.6Hz, 1H, Ar-H), 7.60 (s, 1H, Ar-H), 7.53 (s, 1H, Ar- H), 7.37 (s, 1H, Ar-H), 7.20 (s, 1H, Ar-H), 6.06 (s, 1H, COCHCl2), 4.32 [s, 1H, ArCH 2P+(C8H17)3], 4.30 [s, 1H, ArCH 2P+(C8H17)3], 2.24 [m, 6H, ArCH2 P+ (CH 2C7H15)3] , 1.60-1.50 [m, 6H, 3×P+(CH2CH 2C6H13)3], 1.46-1.24 [m, 30H, 3×P+ (C2H4C5 H 10CH3)3], 0.86(t, J=7.2Hz, 9H, CH3); 13C NMR (400 MHz, CDCl3) δ: 192.3, 181.1, 167.4, 162.9, 162.7, 138.7, 137.7, 134.4, 133.1, 125.5, 125.3, 120.51, 120.47, 115.7, 115.6, 65.4, 37.1, 31.9, 31.7, 31.6, 31.0, 30.8, 30.6, 30.0, 29.7, 29.4, 29.0, 28.9, 28.8, 22.7, 22.6, 21.6, 21.3, 19.1, 18.6,14.1; LC-MS (ESI) m/z: (M-Br)+ 733.67.
Application Example 1
Aloe-emodin quaternary alkylphosphonium salt dichloroacetic acid ester is to lung cell A549 proliferation inhibition test
By the A549 cells of logarithmic phase, after being digested with pancreatin, cell count, 5 × 10 are made into4-1×105/ ml cell is dense Degree, by obtained cell suspension, 96 orifice plates are inoculated into per the μ L of hole 100, are put in 37 DEG C, 5% CO224 h are cultivated in incubator, are abandoned Fall old culture medium, add the various concentrations aloe-emodin quaternary alkylphosphonium salt dichloroacetic acid ester medicine prepared, act on 24 h respectively Afterwards, inhale and abandon pastille culture medium, the 0.5 mg/ml MTT μ L of solution 100 are added in every hole, continue after being incubated 4 h, terminate training Support;Careful inhale abandons supernatant in 96 orifice bores, and 100 μ L DSMO are added per hole, vibrates 10min, is in enzyme in 570 nm wavelength Each hole absorbance value is determined on mark instrument(OD values), calculate cell survival rate(%)=(Medication group mean OD value/blank control group is average OD values)×100%.Data processing and calculation of half inhibitory concentration IC are carried out with GraphPad Prism softwares50Value, as a result as schemed Shown in 2.
Application Example 2
Aloe-emodin quaternary alkylphosphonium salt dichloroacetic acid ester is to hepatocellular carcinoma H22 proliferation inhibition test
By the HepG2 cells of logarithmic phase, after being digested with pancreatin, cell count, 5 × 10 are made into4-1×105/ ml cell is dense Degree, by obtained cell suspension, 96 orifice plates are inoculated into per the μ L of hole 100, are put in 37 DEG C, 5% CO224 h are cultivated in incubator, are abandoned Fall old culture medium, add the various concentrations aloe-emodin quaternary alkylphosphonium salt dichloroacetic acid ester medicine prepared, act on 24 h respectively Afterwards, inhale and abandon pastille culture medium, the 0.5 mg/ml MTT μ L of solution 100 are added in every hole, continue after being incubated 4 h, terminate Culture;Careful inhale abandons supernatant in 96 orifice bores, and 100 μ L DSMO are added per hole, vibrates 10 min, is in 570 nm wavelength Each hole absorbance value is determined on ELIASA(OD values), calculate cell survival rate(%)=(Medication group mean OD value/blank control group is put down Equal OD values)×100%.Data processing and calculation of half inhibitory concentration IC are carried out with GraphPad Prism softwares50Value.As a result such as Shown in Fig. 3.
The dichloroacetic acid of table 1 and aloe-emodin and its derivative etc. are to lung cell A549 and hepatocellular carcinoma H22 IC50Value(μM).
It is above-mentioned test result indicates that, aloe-emodin quaternary alkylphosphonium salt dichloroacetic acid ester is because can to produce aloe big after hydrolysis Flavine quaternary alkylphosphonium salt and glycolytic inhibitor dichloroacetic acid, the mitochondria energy supply and glycolysis energy supply of cancer cell can be destroyed simultaneously, Good anticancer is shown to kinds of tumor cells such as HL-60 cells, lung cell A549 and hepatocellular carcinoma H22 etc. Activity.This result shows that it is good Anti-Cancer Drug Design that dichloroacetic acid and aloe-emodin quaternary alkylphosphonium salt are carried out into covalent bond Thinking.
The foregoing is only presently preferred embodiments of the present invention, all equivalent changes done according to scope of the present invention patent with Modification, it should all belong to the covering scope of the present invention.

Claims (8)

  1. A kind of 1. aloe-emodin quaternary alkylphosphonium salt for suppressing group containing glycolysis, it is characterised in that:Its structural formula is as follows:
  2. 2. a kind of preparation method for the aloe-emodin quaternary alkylphosphonium salt for suppressing group containing glycolysis as claimed in claim 1, its It is characterised by:Aloe-emodin and excessive phosphorus tribromide are reacted, obtain bromo aloe-emodin;Bromo aloe-emodin again with Tri-n-octyl phosphine carries out nucleophilic substitution and obtains aloe-emodin quaternary alkylphosphonium salt;Aloe-emodin quaternary alkylphosphonium salt is sent out with dichloroacetyl chloride Raw esterification obtains aloe-emodin quaternary alkylphosphonium salt dichloroacetic acid ester.
  3. 3. the preparation method of the aloe-emodin quaternary alkylphosphonium salt according to claim 2 for suppressing group containing glycolysis, it is special Sign is:Specifically include following steps:
    1)The synthesis of bromo aloe-emodin:3.70 mmol aloe-emodins are dissolved in 100 mLCCl4In, add at room temperature 10.8 mmol PBr3, 65 DEG C are warming up to, stirred at reflux reacts 24 h;Revolving removes solvent, and residue is through silica gel column chromatography Purifying, obtains bromo aloe-emodin;
    2)The synthesis of aloe-emodin quaternary alkylphosphonium salt:1.00 mmol bromo aloe-emodins are dissolved in 15 mL acetone, added at room temperature Enter 1.12 mmol tri-n-octyl phosphines, be warming up to 50 DEG C, react 6 h, solvent is spin-dried for by reaction after terminating, with dichloromethane wet method Loading, aloe-emodin quaternary alkylphosphonium salt is obtained through silica gel column chromatography gradient elution;
    3)The synthesis of aloe-emodin quaternary alkylphosphonium salt dichloroacetic acid ester:By 0.14 mmol aloe-emodins quaternary alkylphosphonium salt and 1.09 mmol Potassium carbonate is dissolved in there-necked flask with 20 mL acetone, is warming up to 37 DEG C of 0.5 h of stirring, is added 1.05 mmol dichloroacetyl chlorides, stir Mix 3 h of reaction;Stop removing solvent with Rotary Evaporators after reacting, with dichloromethane wet method loading, gradient elution carries out post layer Analysis purification, obtains aloe-emodin quaternary alkylphosphonium salt dichloroacetic acid ester.
  4. 4. the preparation method of the aloe-emodin quaternary alkylphosphonium salt according to claim 3 for suppressing group containing glycolysis, it is special Sign is:Step 1)Middle silica gel column chromatography purifying eluant, eluent used is CH2Cl2
  5. 5. the preparation method of the aloe-emodin quaternary alkylphosphonium salt according to claim 3 for suppressing group containing glycolysis, it is special Sign is:Step 2)The order of middle gradient elution is:V(CH2Cl2):V(C2H5OH)= 40:1→30:1→25:1→20:1。
  6. 6. the preparation method of the aloe-emodin quaternary alkylphosphonium salt according to claim 3 for suppressing group containing glycolysis, it is special Sign is:Step 3)The eluting order of middle gradient elution is:V(CH2Cl2):V(C2H5OH)=40:1→30:1→25:1→20: 1。
  7. 7. a kind of aloe-emodin quaternary alkylphosphonium salt for suppressing group containing glycolysis as claimed in claim 1 is preparing treating cancer Application in medicine.
  8. 8. the aloe-emodin quaternary alkylphosphonium salt according to claim 7 for suppressing group containing glycolysis is preparing treating cancer medicine Application in thing, it is characterised in that:Described cancer includes lung cancer and liver cancer.
CN201610303228.7A 2016-05-10 2016-05-10 Suppress aloe-emodin quaternary alkylphosphonium salt of group and preparation method thereof containing glycolysis Expired - Fee Related CN105859777B (en)

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CN110003021B (en) * 2019-03-16 2022-02-15 福建医科大学附属协和医院 Preparation method of quaternary ammonium salt dichloroacetate with anti-leukemia activity
CN110981909B (en) * 2019-12-27 2021-06-29 福州大学 Copper-containing aloe-emodin quaternary phosphonium salt and synthetic method and application thereof

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103936788A (en) * 2014-02-22 2014-07-23 福州大学 Emodin quaternary phosphonium salt with antitumor activity, and preparation method thereof
CN104987356A (en) * 2015-06-11 2015-10-21 福州大学 Ursolic acid-glycolysis inhibitor DCA conjugate and application thereof

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103936788A (en) * 2014-02-22 2014-07-23 福州大学 Emodin quaternary phosphonium salt with antitumor activity, and preparation method thereof
CN104987356A (en) * 2015-06-11 2015-10-21 福州大学 Ursolic acid-glycolysis inhibitor DCA conjugate and application thereof

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Synthesis and antitumor activity of emodin quaternary ammonium salt derivatives;Jingwei Shao等;《European Journal of Medicinal Chemistry》;20120807;第56卷;第308-319页 *
蒽醌类亲脂性阳离子的合成及抗癌活性;刘丹等;《高等学校化学学报》;20150630;第36卷;第1100-1106页 *

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