CN103356515B - A kind of emodin class anthraquinone derivative is preparing the application in medicines resistant to liver cancer - Google Patents
A kind of emodin class anthraquinone derivative is preparing the application in medicines resistant to liver cancer Download PDFInfo
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Abstract
The invention provides a kind of emodin class anthraquinone derivative and prepare the application in medicines resistant to liver cancer.Described emodin class anthraquinone derivative is Isosorbide-5-Nitrae-dimethyl-6,8-dimethoxy-9,10-anthraquinone.This derivant not only has good suppression hepatoma cell proliferation and induces the effect of its apoptosis, and it is very little to normal cytotoxicity, its can with the coupling of the chemotherapeutics such as 5-FU and cisplatin, increase the sensitivity of chemotherapeutics, reach the effect of inhibition tumor cell growth.It can be used for preparing medicines resistant to liver cancer or adjuvant chemotherapy medicine.
Description
Technical field
The present invention relates to emodin class anthraquinone derivative, be specially Isosorbide-5-Nitrae-dimethyl-6,8-dimethoxy-9,10-anthraquinone and preparing the application in medicines resistant to liver cancer.
Background technology
Hepatocarcinoma (hepatocellularcarcinoma, HCC) be the malignant tumor that a kind of grade malignancy is high, invasion and m etastasis strong, treatment is difficult, mortality rate is high, current China liver cancer patient accounts for the more than half of global hepatocarcinoma patient, serious threat human life.Hepatocarcinoma is all insensitive to chemotherapy and radiation, surgical radical treatment person only can account for 15%, easily early stage transfer and postoperative recurrence.This on the one hand may be relevant with the multidrug resistance gene of hepatoma carcinoma cell, and prior reason is the generation development of hepatocarcinoma is a multifactorial process of multi-step, relates to change biology of intracellular series of complex.Only for single link medicine or treatment can not obtain desirable therapeutic effect.Even if represent the target therapeutic agent in Frontier direction, because its mechanism of action targeting is excessively strong, cause clinical adaptation population few, and very easily occur Drug-resistant and toxicity, do not obtain good efficacy as expected.Therefore, the important directions becoming discipline development for the medicine of the multiple link of tumorigenesis or the innovative treatments of Drug combination of studying multiple different mechanisms is researched and developed.At present, antitumor drug common mechanism comprises Developing restraint, apoptosis-induced and downright bad, differentiation-inducing etc.Regrettably, in medicines resistant to liver cancer conventional at present, most anti-tumor effect is single, and curative effect is also not obvious.Even first-line drug amycin, 5-FU etc. also also exist many-sided problem.Therefore, research and development have the new drug of the multiple anti-tumor function of high-efficiency low-toxicity, or the innovative treatments of exploration multiple medicines use in conjunction is for the country occurred frequently of the such hepatocarcinoma of China, has important theory significance and using value.
Emodin class anthraquinone compounds is the important active component of a naturally occurring class, is present in various plants, as Radix Et Rhizoma Rhei, and Aloe etc.Anthraquinone analog compound have more cause let out, the multiple biological activity such as antibacterial, blood pressure lowering, antioxidation, antitumor, but due to its water solublity low, bioavailability is poor, at present except its discharge function of application, other pharmacologically active also rarely have be applied to clinical.And though emodin class anthraquinone derivative is present in various plants, but because its content in plant is low, extract difficulty, and leaching process more complicated, limit further structure optimization and screening active ingredients, therefore in conjunction with the action principle of antitumor drug and the structure activity relationship of mechanism and anthraquinone derivatives, our design and synthesis 1,4-dimethyl-6,8-dimethoxy-9,10-anthraquinone, preliminary experiment research finds that the activity of its Neuraminidase in Influenza Virus has certain inhibitory action, and it need further investigation preparing cancer therapy drug.
Summary of the invention
A kind of emodin class anthraquinone derivative is the object of the present invention is to provide to prepare the application in medicines resistant to liver cancer.
A kind of emodin class anthraquinone derivative provided by the invention is preparing the application in medicines resistant to liver cancer, described emodin class anthraquinone derivative, and be Isosorbide-5-Nitrae-dimethyl-6,8-dimethoxy-9,10-anthraquinone, its molecular structural formula is:
Its molecular weight is 296.32, and yellow powder compound, dissolves in ethanol, methanol, dimethyl sulfoxide etc.
The preparation of Isosorbide-5-Nitrae-dimethyl-6,8-dimethoxy-9,10-anthraquinone is shown in " synthesis of several anthraquinone derivative and the preliminary study of anti tumor activity in vitro thereof, Su Qiang, Zhang Liwei, 2010, Master's thesis ".
1,4-dimethyl-6,8-dimethoxy-9,10-anthraquinone proves as the application experiment of medicines resistant to liver cancer: act on 48h when compound concentration is 80 μ g/mL and the proliferation inhibition rate of hepatoma H22 cells can be made to reach 81.8%, and be only 6.8% to the proliferation inhibition rate of Human normal hepatocyte HL-7702.And its proliferation function is significant dosage and time-dependent effect, when 24h and 48h, its half suppression ratio IC50 is respectively 39.2 μ g/mL and 63.1 μ g/mL.After DAPI dyeing, fluorescence microscope detects the cohesion of visible stain body, nuclear collapse, and presents irregularly shaped, has a small amount of apoptotic body to produce.Flow cytometry its apoptosis result of hepatoma Hep G 2 cells is shown: cellular control unit apoptosis rate is 6.2%, after compound treated cells 48h with 25 and 80 μ g/mL, apoptosis rate all comparatively matched group obviously raises, be respectively 34.4% and 80.8%, this compound visible can obviously induce hepatoma Hep G 2 cells apoptosis, and there is dose dependent, this is consistent with MTT result.
By 1,4-dimethyl-6,8-dimethoxy-9,10-anthraquinone respectively with chemotherapeutics 5-fluorouracil (5-FU) and cisplatin (DDP) coupling, MTT detects its growth inhibited effect to hepatoma Hep G 2 cells, result show the growth inhibited effect of single medicine to hepatoma Hep G 2 cells the strongest be 1,4-dimethyl-6,8-dimethoxy-9,10-anthraquinone, secondly be DDP, 5-FU.What during drug combination, inhibitory action was the strongest is 1,4-dimethyl-6,8-dimethoxy-9,10-anthraquinone+DDP+5-FU drug combination group, is then followed successively by 1,4-dimethyl-6,8-dimethoxy-9,10-anthraquinone+DDP combines, Isosorbide-5-Nitrae-dimethyl-6,8-dimethoxy-9,10-anthraquinone+5-FU combines, 5-FU+DDP associating.
Compared with prior art, provided by the invention 1,4-dimethyl-6,8-dimethoxy-9,10-anthraquinone is very little to normal cell injury, has obvious cytotoxic effect to hepatoma cell strain, and be better than routine clinical medication 5-FU and DDP of current hepatocarcinoma, its can with the coupling of the chemotherapeutics such as 5-FU and cisplatin, increase the sensitivity of chemotherapeutics, reach the effect of inhibition tumor cell growth.This compound has significant resisting liver cancer activity, can be used for preparing medicines resistant to liver cancer or adjuvant chemotherapy medicine.
Accompanying drawing explanation
Figure 11,4-dimethyl-6,8-dimethoxy-9,10-anthraquinone is to the depression effect figure of several tumor cell line
Isosorbide-5-Nitrae-dimethyl-6,8-dimethoxy-9,10-anthraquinone of Fig. 2 variable concentrations is to the inhibitory effects on proliferation of hepatoma Hep G 2 cells effect 24h and 48h
Fig. 3 fluorescence microscope Isosorbide-5-Nitrae-dimethyl-6,8-dimethoxy-9,10-anthraquinone is to the morphological change of hepatoma Hep G 2 cells, wherein A is matched group hepatoma carcinoma cell, and B is the matched group hepatoma carcinoma cell after DAPI dyeing, and C carries out DAPI dyeing after 50 μ g/mL compound treatment HepG2 cell 48h
Fig. 4 Flow cytometry Isosorbide-5-Nitrae-dimethyl-6,8-dimethoxy-9,10-anthraquinone is on the impact of hepatoma Hep G 2 cells apoptosis, and wherein A is cellular control unit, and B-C is the apoptosis rate after the compound treated cells 48h using 25 and 80 μ g/mL respectively
The ultra-violet absorption spectrum of Figure 51,4-dimethyl-6,8-dimethoxy-9,10-anthraquinone and bovine serum albumin
The fluorescence spectrum of Figure 61,4-dimethyl-6,8-dimethoxy-9,10-anthraquinone and bovine serum albumin
The ultra-violet absorption spectrum of Figure 71,4-dimethyl-6,8-dimethoxy-9,10-anthraquinone and calf thymus DNA
The fluorescence spectrum of Figure 81,4-dimethyl-6,8-dimethoxy-9,10-anthraquinone and calf thymus DNA
Detailed description of the invention
Embodiment 1
Isosorbide-5-Nitrae-dimethyl-6,8-dimethoxy-9,10-anthraquinone Anticancer Activity in vitro is tested:
Active anticancer experiment is realized by cytotoxicity, adopts the standard MTT colorimetric method for determining proliferation inhibition activity of this compound to 7 kinds of tumor cell lines.Tested tumor cell line is HepG2 cell lines, gastric cancer cell, breast cancer cell line mcf-7, cervical cancer cell lines HeLa, cholangiocarcinoma cell strain QBC-939, esophageal cancer cell EC9706, colon cancer cell line SW480, in contrast with Human normal hepatocyte HL-7702 simultaneously.
Concrete steps are: get and be in exponential phase, each cell in good condition, after adding 0.25% trypsinization, make single cell suspension, cell counting count board counts, be inoculated in 96 orifice plates by every hole 100 μ L, every porocyte quantity controls at 5 × 104/mL, 37 DEG C, 5%CO2 incubator incubated overnight, add variable concentrations (the 5-80 μ g/mL) sample prepared, after effect 48h, every hole adds 20 μ lMTT (5mg/mL), continue to cultivate 4h, abandon the every hole of supernatant and add 150 μ LDMSO, vibration 10min, until completely dissolved, the absorbance at 490nm place is measured with enzyme-labeled immunity analyzer (Bio-RadModel550).By following formulae discovery cell proliferation inhibition rate.Suppression ratio=(1 – processed group A value/control group A value) × 100% of Growth of Cells, repeats above experiment three times.
The results show is after concentration is each cell 48h of 80 this compound effects of μ g/mL, compound all has certain inhibited proliferation to tested different tumor cells, wherein responsive strain is hepatocellular carcinoma H22, its suppression ratio reaches 81.8%, to cervical cancer cell lines HeLa, the proliferation inhibition rate of colon cancer cell line SW480 and esophageal cancer cell EC9706 is respectively 71.2%, 65.2% and 61.4%, to breast cancer cell line mcf-7, effective suppression ratio of gastric cancer cell and cholangiocarcinoma cell strain QBC-939 is respectively 47.1%, 42.1% and 36.5%, and 6.8%(is only as shown in Figure 1 to the proliferation inhibition rate of Human normal hepatocyte HL-7702).
When after this compound effects hepatoma Hep G 2 cells 24h and 48h with variable concentrations (5-80 μ g/mL), compound to the inhibited proliferation of hepatoma Hep G 2 cells along with concentration and the increase of time, and strengthen gradually, in significant dosage with time-dependent effect (as shown in Figure 2), its half suppression ratio IC50 is respectively 39.2 μ g/mLL and 63.1 μ g/mL.
When being 40 μ g/mL1 by concentration, 4-dimethyl-6,8-dimethoxy-9,10-anthraquinone respectively with the 5-FU of 10,20 and 40 μ g/mL and cisplatin is alone and drug combination 48h to the inhibitory effects on proliferation of hepatoma Hep G 2 cells, result is as shown in table 1: what the growth inhibited effect of single medicine to hepatoma Hep G 2 cells was the strongest is Isosorbide-5-Nitrae-dimethyl-6,8-dimethoxy-9, secondly 10-anthraquinone is DDP, 5-FU.What during drug combination, inhibitory action was the strongest is 1,4-dimethyl-6,8-dimethoxy-9,10-anthraquinone+DDP+5-FU drug combination group, is then followed successively by 1,4-dimethyl-6,8-dimethoxy-9,10-anthraquinone+DDP combines, Isosorbide-5-Nitrae-dimethyl-6,8-dimethoxy-9,10-anthraquinone+5-FU combines, DDP+5-FU associating.
Table 11,4-dimethyl-6,8-dimethoxy-9,10-anthraquinone respectively with 5-FU and DDP mono-medicine and drug combination to the inhibitory effects on proliferation of hepatoma Hep G 2 cells
n=3，P﹤0.01.
The morphological observation of HepG2 cell
DAPI is a kind of very special DNA stain, and it very rapidly through kytoplasm and its nuclear membrane of cell, can make DNA painted, and can launch blue fluorescence at fluorescence microscopy Microscopic observation.Hepatoma Hep G 2 cells is inoculated in 6 orifice plates, until cell attachment and after well-grown, through the compound treatment 48h of 50 μ g/mL, and with 0.1%DMSO as a control group, collecting cell, be resuspended in fixative with after phosphate buffer solution (20mmol/LPBS, the pH7.2) washing of pre-cooling.After 15min, by suspension low-speed centrifugal, collecting precipitation, buffer solution washes twice, and drips on microscope slide afterwards by cell suspension, with the DAPI lucifuge dyeing 15min of 2 μ g/mL, the morphological change of observation of cell core under fluorescence microscope.As shown in Figure 3, A is matched group hepatoma carcinoma cell, visible cell well-grown under inverted microscope; B is the matched group hepatoma carcinoma cell after DAPI dyeing, and under fluorescence microscope, visible cell nuclear staining is more even; C is with carrying out DAPI dyeing after 50 μ g/mL compound treatment HepG2 cell 48h, and visible stain body condenses, nuclear collapse, and presents irregularly shaped, has a small amount of apoptotic body to produce.
Flow cytometry HepG2 apoptosis rate
In order to detect the impact of this compound on hepatoma cell apoptosis, use respectively 0.1% DMSO and compound effects in hepatoma Hep G 2 cells, after 48h with AnnexinV/FITC and PI dyeing, collecting cell flow cytomery.Result as shown in Figure 4, A is cellular control unit, apoptosis rate is 6.2%, B-C is after the compound treated cells 48h using 25 and 80 μ g/mL respectively, apoptosis rate all comparatively matched group obviously raises, and is respectively 34.4% and 80.8%, and this compound can obviously induce hepatoma Hep G 2 cells apoptosis as seen, and there is dose dependent, this is consistent with MTT result.
The above results shows compound 1,4-dimethyl-6,8-dimethoxy-9,10-anthraquinone very effectively can suppress hepatoma cell proliferation and induce its apoptosis, its can with the chemotherapeutics such as 5-FU and cisplatin synergism, increase the sensitivity of chemotherapeutics, reach the effect of inhibition tumor cell growth, it can be applied preparing in medicines resistant to liver cancer.
The interaction of embodiment 21,4-dimethyl-6,8-dimethoxy-9,10-anthraquinone and bovine serum albumin
Absorption Spectrum Research
Fig. 5 curve 1 is the ultra-violet absorption spectrum of bovine serum albumin, curve 2-10 is the ultra-violet absorption spectrum after adding this compound of variable concentrations in bovine serum albumin, as seen from the figure when the absorption peak strength of bovine serum albumin after the compound adding variable concentrations strengthens.Show to exist between compound and BSA to interact, define the complex with certain stability.
Compound is on the impact of bovine serum albumin fluorescence spectrum
Fig. 6 curve 1 is the fluorescence spectrum of bovine serum albumin, curve 2-10 is the fluorescence spectrum after adding this compound of variable concentrations in bovine serum albumin, the regular reduction of fluorescence intensity of the bovine serum albumin as seen from the figure after adding this compound of variable concentrations, illustrates that compound has the broken effect of going out of fluorescence to BSA.The reduction of fluorescence intensity is owing to there occurs caused by the complex that interacts and generate non-fluorescence class between this compound and serum albumin, and along with the continuous increase of drug level, the binding site of medicine on albumen is constantly occupied, reach capacity gradually, so the degree causing fluorescence intensity to reduce is more and more less.Judge that the fluorescent quenching process of this compound to BSA may be a static quenching process according to quencher slope of a curve and straight slope.
The interaction of embodiment 31,4-dimethyl-6,8-dimethoxy-9,10-anthraquinone and DNA is tested
Absorption Spectrum Research
Fig. 7 curve 1 is the ultra-violet absorption spectrum of DNA, and curve 2-9 is the ultra-violet absorption spectrum after this compound adding variable concentrations in DNA, as seen from the figure when DNA absorption peak strength after the compound adding variable concentrations declines.According to bibliographical information, when micromolecule is incorporated between CT-DNA Double helix base pair with embedded mode, its absorption spectrum shows hypochromic effect, red shift of wavelength; When micromolecule for electrostatically or groove binding is incorporated into CT-DNA time, its absorption spectrum shows hyperchromicity or loses lustre not obvious, does not have red shift; Therefore, the interaction of compound now and between CT-DNA should based on embedded mode.
Compound is on the impact of DNA fluorescence spectrum
Fig. 8 curve 1 is the fluorescence spectrum of DNA, curve 2-10 is the fluorescence spectrum after the compound adding variable concentrations in DNA, as seen from the figure when the Fluorescence Increasing of DNA after the compound adding variable concentrations, and the amplitude of fluorescence intensity increase and the concentration of compound have good linear relationship.Fluorescent spectrometry is a kind of desirable method of research micromolecule and nucleic acid interaction, after micromolecular compound inserts DNA base pair, the rigidity of DNA is increased, shows Fluorescence Increasing.Therefore, we judge that this compound is with inserted mode Interaction with DNA, and this is consistent with ultra-violet absorption spectrum acquired results.
Above-mentioned experimental result illustrates that this compound is by acting on serum albumin and DNA and reaching the object of anti-hepatocarcinoma.
Claims (1)
1.1,4-dimethyl-6,8-dimethoxy-9,10-anthraquinone and antitumor drug 5-FU and cisplatin combinedly preparing the application in medicines resistant to liver cancer.
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| Title |
|---|
| 几种蒽醌衍生物的合成及其体外抗肿瘤;苏强;《豆丁网http://www.docin.com/p-282076181.html》;20111104;摘要，第38页第1段，第50页第1段 * |
| 大黄中蒽醌衍生物的构效关系;宗金锐，等;《中国中药杂志》;20081031;第33卷(第20期);2424-2427 * |
| 大黄素在体外诱导人肝癌细胞HepG2发生凋亡的初步研究;刘剑波，等;《癌症》;20031231;第22卷(第12期);1280-1283 * |
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