CN111410660B - Substituted perxanthenoxanthene compounds and uses thereof - Google Patents
Substituted perxanthenoxanthene compounds and uses thereof Download PDFInfo
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- 150000001875 compounds Chemical class 0.000 title claims description 17
- -1 xanthenoxanthene compound Chemical class 0.000 claims abstract description 15
- 238000006243 chemical reaction Methods 0.000 claims description 23
- 238000002360 preparation method Methods 0.000 claims description 11
- 239000000758 substrate Substances 0.000 claims description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- 239000007787 solid Substances 0.000 claims description 9
- 239000003054 catalyst Substances 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 6
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 6
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 6
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 6
- 201000010881 cervical cancer Diseases 0.000 claims description 6
- 206010017758 gastric cancer Diseases 0.000 claims description 6
- 201000005202 lung cancer Diseases 0.000 claims description 6
- 208000020816 lung neoplasm Diseases 0.000 claims description 6
- 201000011549 stomach cancer Diseases 0.000 claims description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- 201000007270 liver cancer Diseases 0.000 claims description 4
- 208000014018 liver neoplasm Diseases 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
- 239000007795 chemical reaction product Substances 0.000 claims description 3
- 239000003480 eluent Substances 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 239000003208 petroleum Substances 0.000 claims description 3
- 239000002994 raw material Substances 0.000 claims description 3
- 238000010898 silica gel chromatography Methods 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- 238000005303 weighing Methods 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 2
- 239000003560 cancer drug Substances 0.000 claims 4
- CZGUXPBIKCUWLE-UHFFFAOYSA-N 10,23-dioxahexacyclo[12.12.0.02,11.04,9.015,24.017,22]hexacosa-1(26),2,4,6,8,11,13,15,17,19,21,24-dodecaene Chemical class C12=CC=C3OC4=CC=CC=C4C=C3C1=CC=C1C2=CC2=CC=CC=C2O1 CZGUXPBIKCUWLE-UHFFFAOYSA-N 0.000 abstract description 14
- 239000002246 antineoplastic agent Substances 0.000 abstract description 6
- 229940041181 antineoplastic drug Drugs 0.000 abstract description 6
- 230000000259 anti-tumor effect Effects 0.000 abstract description 4
- 210000004027 cell Anatomy 0.000 description 27
- 239000000047 product Substances 0.000 description 13
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 12
- 239000003814 drug Substances 0.000 description 10
- 230000004083 survival effect Effects 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 230000035484 reaction time Effects 0.000 description 6
- JWAZRIHNYRIHIV-UHFFFAOYSA-N 2-naphthol Chemical compound C1=CC=CC2=CC(O)=CC=C21 JWAZRIHNYRIHIV-UHFFFAOYSA-N 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 238000002428 photodynamic therapy Methods 0.000 description 4
- 206010034972 Photosensitivity reaction Diseases 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- QDLAGTHXVHQKRE-UHFFFAOYSA-N lichenxanthone Natural products COC1=CC(O)=C2C(=O)C3=C(C)C=C(OC)C=C3OC2=C1 QDLAGTHXVHQKRE-UHFFFAOYSA-N 0.000 description 3
- 208000007578 phototoxic dermatitis Diseases 0.000 description 3
- 231100000018 phototoxicity Toxicity 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 230000003698 anagen phase Effects 0.000 description 2
- 229950011260 betanaphthol Drugs 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000012679 serum free medium Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 231100000002 MTT assay Toxicity 0.000 description 1
- 238000000134 MTT assay Methods 0.000 description 1
- ZXFRXCVMPUDSAF-UHFFFAOYSA-N N#CC(C=C1)=CC2=C1OC1=CC=C3C4=CC5=CC=CC=C5OC4=CC=C3C1=C2 Chemical compound N#CC(C=C1)=CC2=C1OC1=CC=C3C4=CC5=CC=CC=C5OC4=CC=C3C1=C2 ZXFRXCVMPUDSAF-UHFFFAOYSA-N 0.000 description 1
- REAYFGLASQTHKB-UHFFFAOYSA-N [2-[3-(1H-pyrazol-4-yl)phenoxy]-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound N1N=CC(=C1)C=1C=C(OC2=NC(=CC(=C2)CN)C(F)(F)F)C=CC=1 REAYFGLASQTHKB-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 150000001491 aromatic compounds Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- AMDQVKPUZIXQFC-UHFFFAOYSA-N dinaphthylene dioxide Chemical compound O1C(C2=C34)=CC=CC2=CC=C3OC2=CC=CC3=CC=C1C4=C32 AMDQVKPUZIXQFC-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000005525 hole transport Effects 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 231100000820 toxicity test Toxicity 0.000 description 1
- 230000004565 tumor cell growth Effects 0.000 description 1
- 150000003732 xanthenes Chemical class 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/06—Peri-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The present invention discloses substituted xanthenoxanthene compounds of formula I. The substituted xanthenoxanthene compound provided by the invention has high antitumor activity and good prospect in preparing antitumor drugs.
Wherein R is1Selected from H, CN, COOCH3Or CONHCH2CH2OH，R2Selected from CN or COOCH3Or CONHCH2CH2OH。
Description
The technical field is as follows:
the invention relates to a compound with anticancer activity and the application field thereof, in particular to a substituted xanthene compound and the application thereof.
Background art:
photodynamic therapy (PDT) is an emerging medical discipline under research and development for the treatment of tumors and other benign diseases, and is a new therapy for tumors following traditional therapies for tumors such as surgery, radiotherapy, chemotherapy and immunotherapy.
The Xanthenoxanthene (peri-Xanthenoxanthene) is a condensed ring aromatic compound, can emit blue fluorescence, is a compound with strong fluorescence, and is a hole transport material with great potential, can be applied to OLEDs, and is expected to develop applications thereof in other fields.
The invention content is as follows:
the invention aims to provide a substituted xanthenoxanthene compound and application thereof, in particular to synthesis of the substituted xanthenoxanthenoxanthene compound and application thereof in preparing antitumor drugs, wherein the substituted xanthenoxanthenoxanthenoxanthenoxantheno compound has strong in-vitro photoperiod inhibition activity on human cervical cancer cells, human lung cancer cells, human gastric cancer cells and human liver cancer cells, has low dark toxicity, and is expected to be applied to photodynamic therapy of tumors.
The invention is realized by the following technical scheme:
a substituted xanthenoxanthene compound of formula I:
wherein R is1Selected from H, CN, COOCH3Or CONHCH2CH2OH，R2Selected from CN or COOCH3Or CONHCH2CH2OH。
The substituted xanthenoxanthene compounds of formula I are shown in Table 1:
the invention also provides a preparation method of the substituted perxanthene xanthene compound, and the reaction equation is as follows:
the method comprises the following steps: weighing reaction substrate and catalyst Cu (OAc)2Controlling the mass ratio of the reaction substrate to the catalyst to be 2:3, uniformly mixing the reaction substrate and the catalyst, placing the mixture into a small beaker, covering the small beaker by a surface dish, and then placing the small beaker into a container filled with carbon powderPutting the beaker in a microwave oven for reaction; and tracking the reaction by TLC (thin layer chromatography) until a reaction substrate disappears, adding a proper amount of water, filtering, drying filter residues, separating and purifying the obtained filter residues by using silica gel column chromatography, and taking a mixture of petroleum ether and ethyl acetate as an eluent to obtain yellow powdery solid, namely the reaction product.
In the reaction substrate
And
the mass ratio of (A) to (B) is 1: 1.
The 2-naphthol is used as a raw material, a series of novel substituted xanthene is obtained by solid phase synthesis under microwave radiation, and is innovatively applied to anti-tumor research, so that the 2-naphthol has strong in-vitro illumination proliferation inhibition activity on human cervical cancer cells, human lung cancer cells, human gastric cancer cells and human liver cancer cells, has low dark toxicity, and is expected to be applied to photodynamic therapy of tumors.
The invention also protects the application of the substituted xanthenoxanthene compound shown in the formula I in the preparation of antitumor drugs.
Preferably, the use of a substituted xanthenoxanthene compound in the manufacture of a medicament for the treatment of cervical cancer.
Preferably, the use of a substituted perxanthenoxanthene compound in the manufacture of a medicament for the treatment of lung cancer.
Preferably, the use of a substituted perxanthenoxanthene compound in the manufacture of a medicament for the treatment of gastric cancer.
Preferably, the use of a substituted xanthenoxanthene compound in the preparation of a medicament against liver cancer.
The invention also protects the application of a pharmaceutically acceptable pharmaceutical composition or preparation formed by the substituted xanthenoxanthene compound and pharmaceutically acceptable salts thereof in preparing antitumor drugs. A pharmaceutical composition comprising as active ingredient at least one substituted perxanthenoxanthene compound of formula I, alone or in combination with one or more pharmaceutically acceptable, inert, non-toxic excipients or carriers.
The invention has the beneficial effects that:
(1) the substituted xanthenoxanthene compound has high antitumor activity and good prospect in preparing antitumor drugs.
(2) The preparation method of the substituted perixanthenoxanthene compound is simple, the reaction condition is mild, the speed is high, and the yield is high.
The specific implementation mode is as follows:
the following is a further description of the invention and is not intended to be limiting. Unless otherwise specified, the experimental materials and reagents in the invention are all conventional commercial products in the technical field.
When the substituted xanthenoxanthene is a mono-substituted xanthenoxanthene, the reaction equation is:
R1＝H，R2＝CN，COOCH3，CONHCH2CH2OH；
when the substituted xanthenoxanthene is a disubstituted xanthenoxanthene, the reaction equation is:
R1＝R2＝CN，COOCH3，CONHCH2CH2OH。
the substituted xanthenoxanthene compounds are prepared as follows: weighing reaction substrate and catalyst Cu (OAc)2Controlling the mass ratio of the mass sum of the reaction substrate to the catalyst to be 2:3,
and
is mixed evenly and placed in the mixture according to the mass ratio of 1:1The small beaker is covered by a watch glass, and then put into a big beaker filled with carbon powder to be put into a microwave oven for reaction. And tracking the reaction by TLC (thin layer chromatography) until the raw materials disappear, adding a proper amount of water, filtering, drying the filter residue, separating and purifying the obtained filter residue by using a silica gel column chromatography, and taking a mixture of petroleum ether and ethyl acetate as an eluent to obtain a yellow powdery solid, namely the reaction product.
Example 1: 3-Cyanoxanthenoxanthene (Compound 1)
The structural formula of the product is as follows:
the reaction time was 8.0min, the product was a yellow solid, and the yield was 57.8% as in the above preparation procedure.
mp 323.6℃；1H NMR(500MHz,DMSO-d6)δ:7.88(s,1H),7.65-7.63(d,J＝9.5Hz,1H),7.57-7.55(d,J＝9.5Hz,1H),7.30-7.21(m,4H),7.16-7.14(d,J＝9Hz,1H),7.08(s,1H),6.83-6.81(d,J＝7.5Hz,1H).IR(KBr)ν:3444.5,3053.1,2930.9,1637.4,1465.8,1270.4,1246.8,1077.6,821.6,775.9,614.6cm-1.HRMS calcd for C21H9NO2[M+H]+307.06333,found 307.06258。
Example 2: 3-Methoxycarbonylphenoxanthenoxanthene (Compound 2)
The structural formula of the product is as follows:
the reaction time was 6.0min, the product was a yellow solid, the yield was 61.2% as in the above preparation.
mp 272.2℃；1H NMR(500MHz,DMSO-d6)δ:7.99(s,1H),7.75-7.73(d,J＝9Hz,1H),7.55-7.53(d,J＝9Hz,1H),7.30-7.28(d,J＝8Hz,1H),7.23-7.20(q,J＝16Hz,2H),7.15-7.13(d,J＝10.5Hz,1H),6.82-6.80(d,J＝7Hz,1H),3.88(s,3H).IR(KBr)ν:2375.7,1716.9,1466.5,1302.5,1206.0,1071.0,806.3,729.5,588.5cm-1.HRMS calcd for C22H12O4[M+H]+340.07356,found 340.07283。
Example 3: 3- (N-hydroxyethyl carboxamido) xanthenoxanthene (Compound 3)
The structural formula of the product is as follows:
the reaction time was 9.0min, the product was a yellow solid, and the yield was 55.3% as in the above preparation procedure.
mp 253.4℃；1H NMR(500MHz,DMSO-d6)δ:8.42(s,1H),7.75(d,J＝1Hz,1H),7.55-7.53(d,J＝9.5Hz,1H),7.47-7.45(d,J＝9Hz,1H),7.17-7.15(d,J＝8Hz,1H),7.12-7.05(m,4H),6.74-6.73(d,J＝7Hz,1H),4.70(s,1H),350-3.48(d,J＝6Hz,2H).IR(KBr)ν:3398.8,3346.5,1629.7,1547.9,1466.0,1335.7,1252.2,1077.6,1053.0,811.6,759.8,525.9cm-1.HRMS calcd for C23H15NO4[M+H]+370.10794,found 370.10896。
Example 4: 3, 9-Dicyanofexanxanthene (Compound 4)
The structural formula of the product is as follows:
the reaction time was 10.0min, the product was a yellow solid, and the yield was 89.6% as in the above preparation procedure.
mp>400℃；1H NMR(500MHz,DMSO-d6)δ:7.81-7.80(d,J＝7Hz,2H),7.52-7.50(d,J＝9Hz,2H),7.09-7.07(d,J＝9Hz,2H),6.87(s,2H).IR(KBr)ν:3423.6,2365.1,1618.8,1499.7,1460.5,1264.1,1076.8,807.2,668.5,569.4cm-1.HRMS calcd for C22H8N2O2[M+H]+332.05858,found 332.05804。
Example 5: 3, 9-Dimethoxycarbonyl-s-xanthenoxanthene (Compound 5)
The structural formula of the product is as follows:
the reaction time is 12.0min, the product is yellow solid, and the yield is 85.3 percent.
mp 261.0℃；1H NMR(500MHz,DMSO-d6)δ:8.21(s,2H),7.98-7.96(d,J＝8.5Hz,2H),7.31-7.29(d,J＝9Hz,2H),6.87-6.85(d,J＝9Hz,2H).3.89(s,6H).IR(KBr)ν:2958.2,1642.4,1394.1,1286.1,1214.7,1092.0,1075.5,996.6,808.1,759.5,539.8cm-1.HRMS calcd for C24H14O6[M+H]+398.07904,found 398.07823。
Example 6: 3, 9-bis (N-hydroxyethyl carboxamido) xanthenoxanthene (Compound 6)
The structural formula of the product is as follows:
the reaction time was 12.0min, the product was a yellow solid, and the yield was 84.2% as in the above preparation procedure.
mp 251.6℃；1H NMR(500MHz,DMSO-d6)δ:8.41-8.40(d,J＝5.5Hz,2H),7.81(s,2H),7.63-7.61(d,J＝9Hz,2H),7.20-7.18(d,J＝9Hz,4H),4.67-4.65(t,J＝11.5Hz,1H),3.56-3.53(dd,J＝63Hz,4H),3.38-3.35(t,J＝12Hz,2H).IR(KBr)ν:3347.7,1712.5,1654.6,1500.41,287.9,1251.8,1076.7,810.4,759.1,543.6cm-1.HRMS calcd for C26H20N2O6[M+H]+456.13214,found 456.13172。
Example 7: test for antitumor Activity of substituted Comxanthoxanthene Compound 1-6
MTT assay was used to detect the inhibition of tumor cell growth in vitro by the substituted xanthenoxanthene compounds obtained in examples 1-6.
Dark toxicity test: respectively selectScreening human cervical cancer cell strain HeLa, human lung cancer cell A549, human gastric cancer cell strain SGC-7901 and human hepatoma cell Bel-7402. The specific method comprises the following steps: each tumor cell strain in logarithmic growth phase is expressed by 8 multiplied by 104Inoculating the cell amount of each well into a 96-well plate, placing the plate in an incubator for incubation for 24h, changing culture solution, and adding each drug with concentration gradient to make the final concentration of the drug be 10-6～10-4And (3) mol/L, setting 3 parallel multiple holes in each group, and setting a culture solution blank control hole. Then, the mixture was incubated in an incubator for 48 hours, 90. mu.L of a serum-free medium and 10. mu.L of MTT solution at a concentration of 5mg/mL were added to each well, and then the mixture was incubated in the incubator for 4 hours, added to a 100. mu.L DMSO micro-shaker, and shaken for 15 minutes, and then the absorbance was measured at 490nm using a microplate reader. Cell survival was calculated as follows: cell survival (%) × 100% (experimental)/blank). Drawing a cell growth curve by the concentration of each group of medicines and the corresponding cell survival rate, and reading out the concentration of a compound corresponding to the cell survival rate of 50%, wherein the concentration is IC50Values (Dark), see table 2.
Phototoxicity test: respectively selecting and screening a human cervical cancer cell strain HeLa, a human lung cancer cell A549, a human gastric cancer cell strain SGC-7901 and a human hepatoma cell Bel-7402. The specific method comprises the following steps: each tumor cell strain in logarithmic growth phase is expressed by 8 multiplied by 104Inoculating the cell amount of each well into a 96-well plate, placing the plate in an incubator for incubation for 24h, changing culture solution, and adding each drug with concentration gradient to make the final concentration of the drug be 10-6～10-4And (3) mol/L, setting 3 parallel multiple holes in each group, and setting a culture solution blank control hole. The cells were irradiated with white light for 1h, incubated in an incubator for 48h, and 90. mu.L of serum-free medium and 10. mu.L of 5mg/mL MTT solution were added to each well, followed by incubation in an incubator for 4h, shaking in a 100. mu.L DMSO micro shaker for 15min, and then absorbance was measured at 490nm using a microplate reader. Cell survival was calculated as follows: cell survival (%) × 100% (experimental)/blank). Plotting the concentration of each group of drugs and the corresponding cell survival rate to obtain a cell growth curve, and reading out the compound concentration corresponding to the cell survival rate of 50%, which isThe concentration is IC50Values (Light), see table 2 for results.
TABLE 2 in vitro cytotoxicity (IC) of substituted xanthenoxanthene Compounds 1-650，μmol/L)
As can be seen from Table 2, the IC of compounds 1-6 on four tumor cells50Values (Dark) are all>100. mu. mol/L, which indicates that they have extremely low dark toxicity; meanwhile, the compounds 1 to 6 show high phototoxicity to four tumor cells, particularly the compound 3, and the phototoxicity to Heal and Bel-7402 is 0.091 mu mol/L and 0.074 mu mol/L respectively. The results show that the compounds 1-6 are potential PDT antitumor drugs.
The detailed description is specific to possible embodiments of the invention, which are not intended to limit the scope of the invention, but rather are intended to include equivalent implementations or modifications within the scope of the invention.
Claims (4)
1. A substituted xanthenoxanthene compound of formula I:
wherein R is1Selected from H, CN, COOCH3Or CONHCH2CH2OH，R2Selected from CN, COOCH3Or CONHCH2CH2OH。
2. The substituted xanthenoxanthene compound of claim 1 wherein said substituted xanthenoxanthene compound of formula i is as shown in the table:
3. the process for preparing a substituted xanthenoxanthene compound of claim 1 wherein the reaction equation is as follows:
the method comprises the following steps: weighing reaction substrate and catalyst Cu (OAc)2Controlling the mass ratio of the reaction substrate to the catalyst to be 2:3, uniformly mixing the reaction substrate and the catalyst, placing the mixture into a reaction container, placing the reaction container into a container filled with carbon powder, placing the container into a microwave oven for reaction, tracking the reaction by TLC until the raw materials disappear, adding water for filtration, separating and purifying the obtained filter residue by using a silica gel column chromatography, and obtaining yellow powdery solid, namely the reaction product, by using a mixture of petroleum ether and ethyl acetate as an eluent.
4. The use of the substituted perxanthenoxanthene compound according to claim 1 or 2 for the preparation of an anti-cervical cancer drug, an anti-lung cancer drug, an anti-gastric cancer drug or an anti-liver cancer drug.
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