CN101434524B - 4-(4-羟基-3-甲氧基苯亚甲基)姜黄素及其制备方法和在制备抗癌药物的应用 - Google Patents
4-(4-羟基-3-甲氧基苯亚甲基)姜黄素及其制备方法和在制备抗癌药物的应用 Download PDFInfo
- Publication number
- CN101434524B CN101434524B CN 200810071178 CN200810071178A CN101434524B CN 101434524 B CN101434524 B CN 101434524B CN 200810071178 CN200810071178 CN 200810071178 CN 200810071178 A CN200810071178 A CN 200810071178A CN 101434524 B CN101434524 B CN 101434524B
- Authority
- CN
- China
- Prior art keywords
- curcumine
- hydroxy
- cell
- curcumin
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 title claims abstract description 63
- 229940109262 curcumin Drugs 0.000 title abstract description 9
- 235000012754 curcumin Nutrition 0.000 title abstract description 6
- 239000004148 curcumin Substances 0.000 title abstract description 6
- VFLDPWHFBUODDF-UHFFFAOYSA-N diferuloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-UHFFFAOYSA-N 0.000 title abstract description 6
- 239000003814 drug Substances 0.000 title description 8
- 238000002360 preparation method Methods 0.000 title description 5
- 230000001093 anti-cancer Effects 0.000 title 1
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 9
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 claims description 29
- 206010009944 Colon cancer Diseases 0.000 claims description 3
- 239000002246 antineoplastic agent Substances 0.000 claims description 3
- 229940041181 antineoplastic drug Drugs 0.000 claims description 3
- LHGVFZTZFXWLCP-UHFFFAOYSA-N guaiacol Chemical compound COC1=CC=CC=C1O LHGVFZTZFXWLCP-UHFFFAOYSA-N 0.000 claims description 3
- 208000014018 liver neoplasm Diseases 0.000 claims description 3
- 201000000498 stomach carcinoma Diseases 0.000 claims description 3
- 208000019838 Blood disease Diseases 0.000 claims description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 2
- 201000010989 colorectal carcinoma Diseases 0.000 claims description 2
- 208000014951 hematologic disease Diseases 0.000 claims description 2
- 208000018706 hematopoietic system disease Diseases 0.000 claims description 2
- 201000007270 liver cancer Diseases 0.000 claims description 2
- 201000000849 skin cancer Diseases 0.000 claims description 2
- 201000008261 skin carcinoma Diseases 0.000 claims description 2
- 210000004027 cell Anatomy 0.000 abstract description 27
- 150000001875 compounds Chemical class 0.000 abstract description 19
- 210000004881 tumor cell Anatomy 0.000 abstract description 10
- 230000000694 effects Effects 0.000 abstract description 9
- 230000005764 inhibitory process Effects 0.000 abstract description 5
- 230000035755 proliferation Effects 0.000 abstract description 5
- 238000009833 condensation Methods 0.000 abstract description 3
- 230000005494 condensation Effects 0.000 abstract description 3
- 238000001727 in vivo Methods 0.000 abstract description 3
- 230000000118 anti-neoplastic effect Effects 0.000 abstract description 2
- 230000015572 biosynthetic process Effects 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 9
- 244000309466 calf Species 0.000 description 8
- 235000015097 nutrients Nutrition 0.000 description 8
- 210000002966 serum Anatomy 0.000 description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 230000000259 anti-tumor effect Effects 0.000 description 5
- 230000000452 restraining effect Effects 0.000 description 5
- 241001529936 Murinae Species 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 201000001441 melanoma Diseases 0.000 description 4
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 4
- 235000012141 vanillin Nutrition 0.000 description 4
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 230000003187 abdominal effect Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 150000003053 piperidines Chemical class 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 235000001018 Hibiscus sabdariffa Nutrition 0.000 description 2
- 235000005291 Rumex acetosa Nutrition 0.000 description 2
- 240000007001 Rumex acetosella Species 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 102000018594 Tumour necrosis factor Human genes 0.000 description 2
- 108050007852 Tumour necrosis factor Proteins 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 230000020411 cell activation Effects 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 229940125782 compound 2 Drugs 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 235000003513 sheep sorrel Nutrition 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- VEEGZPWAAPPXRB-BJMVGYQFSA-N (3e)-3-(1h-imidazol-5-ylmethylidene)-1h-indol-2-one Chemical compound O=C1NC2=CC=CC=C2\C1=C/C1=CN=CN1 VEEGZPWAAPPXRB-BJMVGYQFSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
- 229940123407 Androgen receptor antagonist Drugs 0.000 description 1
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 1
- 206010019695 Hepatic neoplasm Diseases 0.000 description 1
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
- 102000003945 NF-kappa B Human genes 0.000 description 1
- 108010057466 NF-kappa B Proteins 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 239000003936 androgen receptor antagonist Substances 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 229940121369 angiogenesis inhibitor Drugs 0.000 description 1
- 230000003527 anti-angiogenesis Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 208000010749 gastric carcinoma Diseases 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000005040 ion trap Methods 0.000 description 1
- JVTZFYYHCGSXJV-UHFFFAOYSA-N isovanillin Chemical compound COC1=CC=C(C=O)C=C1O JVTZFYYHCGSXJV-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007962 solid dispersion Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
本发明涉及合成抗肿瘤药物,具体涉及合成4-(4-羟基-3-甲氧基苯亚甲基)姜黄素以及其用途。该化合物由姜黄素与香兰醛经Knovenagel缩合制得。本发明化合物4-(4-羟基-3-甲氧基苯亚甲基)姜黄素对多种肿瘤细胞均有明显抑制,尤其是对K562、B16、HepG2、SW480、SH-SY5Y细胞,该化合物对它们的增殖抑制作用明显比Cur的好,其半数抑制浓度约为Cur的1/9。该化合物能明显抑制在体B16肿瘤的大小及重量。
Description
技术领域
本发明涉及合成抗肿瘤药物,具体涉及合成4-(4-羟基-3-甲氧基苯亚甲基)姜黄素以及其用途。
背景技术
姜黄素(姜黄素curcumin,简称Cur)在印度、中国、日本、韩国等地有上千年的食用和药用记载。目前国内外研究发现姜黄素具有抗肿瘤、抗炎、抗血管生成、抗氧化和神经保护等多种活性。但是姜黄素水溶性差,其水溶液不稳定,尤其在中性至碱性pH值条件下更不稳定,姜黄素口服后在体内代谢快,生物利用度低,血药浓度较低,已成为限制其临床应用的主要因素。通过结构改造合成姜黄素衍生物,增强活性、水溶性有重要意义。目前姜黄素类似物抗肿瘤方面国外专利授权的有:Vander Jagt等用对NF-κB和AP-1因子抑制,筛选抗肿瘤活性姜黄素类似物(US20070060644),Lee等的雄激素受体拮抗剂姜黄素类似物(US006790979),Snyder等的抗肿瘤和抗血管生成活性姜黄素类似物(US006664272)。
国内外对姜黄素的结构改造路线主要有:改变苯环上取代基种类和位置、β-二酮缩合或为单酮、改变中间不饱和共扼连接链、还原不饱和双键、4位活泼亚甲基取代等,对活性研究仍处于体外实验阶段。
与本发明化合物4-(4-羟基-3-甲氧基苯亚甲基)姜黄素最接近的文献有:Zambre,A.P等(Bioorg.Med.Chem.2006,14,7196-7204)合成了4-(2-羟基苯亚甲基)、4-(2,3-二羟基苯亚甲基)、4-(3,4-二羟基苯亚甲基)姜黄素(依次为化合物2,3,4),评价了以上化合物抑制人白血病细胞KBM-5的活性(该细胞由肿瘤坏死因子诱导细胞核转录因子活化和增殖),以及对肿瘤细胞Jurkat,H1299,and MM1的抑制活性,但以上化合物活性均比姜黄素要低。
本发明通过在姜黄素母体4位引入活性结构单元3,4-二取代苯亚甲基合成新的姜黄素类似物,并评价其抗肿瘤活性。
发明内容
本发明的目的之一在于提供4-(4-羟基-3-甲氧基苯亚甲基)姜黄素,其结构式为:
本发明的目的之二,在于提供4-(4-羟基-3-甲氧基苯亚甲基)姜黄素的制备方法。
本发明化合物4-(4-羟基-3-甲氧基苯亚甲基)姜黄素由姜黄素与香草醛经Knovenagel缩合制得。
具体而言,姜黄素,香草醛,甲醇,加入催化量哌啶,室温下搅拌反应,浓缩移去溶剂,残余物用硅胶柱色谱分离纯化,得红褐色粉末。其反应过程示意式如下:
本发明目的之三在于提供4-(4-羟基-3-甲氧基苯亚甲基)姜黄素,用于制备抗肿瘤药物的应用。
4-(4-羟基-3-甲氧基苯亚甲基)姜黄素,可用于但不局限于制备治疗白血病、皮肤癌、胃癌、结肠癌、肝癌、乳腺癌或***癌药物。
与本发明化合物4-(4-羟基-3-甲氧基苯亚甲基)姜黄素结构、活性最接近的文献有:Zambre,A.P等(Bioorg.Med.Chem.2006,14,7196-7204)合成了4-(2-羟基苯亚甲基)、4-(2,3-二羟基苯亚甲基)、4-(3,4-二羟基苯亚甲基)姜黄素(依次为化合物2,3,4),评价了以上化合物抑制人白血病细胞KBM-5的活性(该细胞由肿瘤坏死因子诱导细胞核转录因子活化和增殖),以及对肿瘤细胞Jurkat,H1299,and MM1的抑制活性,但以上化合物活性均比姜黄素要低。
而本发明化合物4-(4-羟基-3-甲氧基苯亚甲基)姜黄素对多种肿瘤细胞均有明显抑制,尤其是对K562、B16、HepG2、SW480、SH-SY5Y细胞,该化合物对它们的增殖抑制作用明显比姜黄素的好,其半数抑制浓度约为姜黄素的1/9。该化合物能明显抑制在体B16肿瘤的大小及重量,而目前国内外类似化合物均未见相关体内活性报道。
具体实施方式
实施例1 4-(4-羟基-3-甲氧基苯亚甲基)姜黄素的合成。
合成原料姜黄素、3-羟基-4-甲氧基苯甲醛(香草醛)、哌啶均为国药集团化学试剂有限公司,试剂均为分析纯。核磁共振波谱仪(mercury-300,美国Varian公司)离子阱质谱仪(DECAX-30000,美国Thermo Finnigan公司);显微熔点仪(X-4,上海精密仪器厂)。
姜黄素2.2g(6mmol),甲醇50ml,加入催化量哌啶,香草醛0.91g(6mmol),室温下搅拌反应48小时,浓缩移去溶剂,残余物用硅胶柱色谱分离纯化,洗脱剂为乙酸乙酯∶石油醚=1∶3,得红褐色粉末0.9克(产率30%)。mp96-98℃,分子式C29H26O8,1H NMR(300MHz,DMSO):δ(ppm)3.72(s,3H,OCH3),3.86(s,6H,2OCH3),6.77-7.17(m,9H,ArH),7.42(d,2H,J=15.0Hz,C2-H和C6-H),7.55(d,2H,J=15.0Hz,C1-H和C7-H),7.96(s,1H,=CH-Ar).ESI-MS m/z[M-H]501.2。
实施例2 4-(4-羟基-3-甲氧基苯亚甲基)姜黄素抑制肿瘤细胞K562,HL-60,B-16,SW480,HepG2,MGC80-3,SH-SY5Y,Bxpc-3的体外生长活性:
2.1.细胞系
K562:人类慢性粒细胞白血病急变细胞系
HL-60:人类急性髓系白血病细胞系
B16:小鼠黑色素瘤B16细胞株。
SW480:人结肠癌细胞
HepG2:人肝肿瘤细胞
MGC80-3:人胃癌细胞
SH-SY5Y:人神经母细胞瘤细胞
Bxpc-3:人胰腺癌细胞
以上细胞均来源于中科院上海细胞库。
2.2细胞培养
细胞培养液配方见表1,细胞在37℃,5%CO2孵育箱中培养,取对数生长期细胞用于增殖、凋亡实验。
表1培养液配方
细胞株 | 培养液 |
K562 | RPM11640培养液+10%小牛血清 |
HL60 | RPM11640培养液+10%小牛血清 |
B16 | RPM11640培养液+10%小牛血清 |
SW480 | DMEM+10%胎牛血清 |
HepG2 | RPM11640培养液+10%小牛血清 |
Bxpc-3 | DMEM+10%胎牛血清 |
MGC80-3 | RPM11640培养液+10%小牛血清 |
SH-SY5Y | RPM11640培养液+10%小牛血清 |
2.3 MTT法观察4-(4-羟基-3-甲氧基苯亚甲基)姜黄素对细胞增殖的抑制作用
将处于对数生长期的细胞,按密度为悬浮细胞50000个/孔、贴壁细胞8000~12000个/孔接种于96孔板里。实验组(贴壁细胞待贴壁后)分别加入不同浓度的4-(4-羟基-3-甲氧基苯亚甲基)姜黄素和姜黄素,对照组不加药,另设空白组,即只加培养基,无细胞,每组设三个平行孔,37℃培养48h,加入5mg/ml的MTT溶液20ul/孔,继续培养4h后,离心弃上清,加入DMSO150ul,振荡10min,充***解后,用全自动酶标仪(美国BIO-RAD公司生产)检测570nm处的吸光度(OD570)值。根据吸光度计算细胞生长抑制率。
细胞生长抑制率=[对照孔OD值-实验孔OD值]/[对照孔OD值-空白孔OD值]×100%
以同一药物的不同浓度对肿瘤细胞生长抑制率作图,可得到剂量反应曲线,根据线性回归方程求出该药物的半数抑制浓度IC50,即细胞存活率减少50%时的药物浓度。
2.4结果
4-(4-羟基-3-甲氧基苯亚甲基)姜黄素能够显著抑制多种人肿瘤细胞的增殖。由表2可以看到,该化合物对本实验中的各种细胞株都表现出比母体姜黄素更强的抑制作用,尤其是K562、HepG2、SW480、SH-SY5Y这四株细胞株,该化合物对它们的增殖抑制作用明显比姜黄素的好,其半数抑制浓度约为姜黄素的1/9。以上结果表明该化合物体外肿瘤细胞增殖抑制作用比其母体姜黄素的抑制作用强。
实施例3腹腔注射对B16黑色素瘤的抑制作用
3.1材料 BALB/C小鼠,6~8wk龄,雌性,体重18g,中国科学院上海动物实验中心提供。小鼠黑色素瘤B16细胞株。4-(4-羟基-3-甲氧基苯亚甲基)姜黄素制成固体分散剂,使用前用生理盐水溶解成所需浓度。
3.2方法
3.2.1荷瘤小鼠模型的建立B16肿瘤细胞传两代以上,调整细胞数至107/ml,0.2mL/只接种于小鼠右前肢皮下,接种2只,待约两周,剥瘤,匀浆,再接种30只。
3.2.2分组共分为2组:接种瘤株24h后的小鼠随机分成2组:I组为生理盐水组(即肿瘤对照组),II组为给药组(剂量为50mg/kg),给药方法为腹腔注射,0.1ml/10g,共给药10天。
3.2.3抑瘤率处死小鼠后剥瘤称瘤质量,计算抑瘤率.肿瘤抑制率(%)=对照组平均瘤质量-给药组平均瘤质量/对照组平均瘤质量×100%。
3.2.4结果
体内移植肿瘤实验亦观察到4-(4-羟基-3-甲氧基苯亚甲基)姜黄素对小鼠黑色素瘤B16有一定的治疗作用。连续腹腔注射4-(4-羟基-3-甲氧基苯亚甲基)姜黄素(50mg/kg/d)10天,观察到4-(4-羟基-3-甲氧基苯亚甲基)姜黄素在体肿瘤的大小及重量受到明显的抑制,抑制率可达到54.1%(见表3)。
表3 4-(4-羟基-3-甲氧基苯亚甲基)姜黄素对小鼠黑色素瘤B16的抑制作用
**P<0.01与对照组比较
Claims (2)
1.式I的4-(4-羟基-3-甲氧基苯亚甲基)姜黄素用于制备抗肿瘤药物的应用
(式I) 。
2.权利要求1所述的4-(4-羟基-3-甲氧基苯亚甲基)姜黄素用于制备抗肿瘤药物的应用,其特征在于:所述治疗的肿瘤是白血病、皮肤癌、胃癌、结肠癌、肝癌。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN 200810071178 CN101434524B (zh) | 2008-06-05 | 2008-06-05 | 4-(4-羟基-3-甲氧基苯亚甲基)姜黄素及其制备方法和在制备抗癌药物的应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN 200810071178 CN101434524B (zh) | 2008-06-05 | 2008-06-05 | 4-(4-羟基-3-甲氧基苯亚甲基)姜黄素及其制备方法和在制备抗癌药物的应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN101434524A CN101434524A (zh) | 2009-05-20 |
CN101434524B true CN101434524B (zh) | 2012-07-25 |
Family
ID=40709178
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN 200810071178 Expired - Fee Related CN101434524B (zh) | 2008-06-05 | 2008-06-05 | 4-(4-羟基-3-甲氧基苯亚甲基)姜黄素及其制备方法和在制备抗癌药物的应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN101434524B (zh) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101830819B (zh) * | 2010-05-26 | 2013-08-28 | 福建医科大学 | 苯丁酰基姜黄素衍生物及其在制备抗肿瘤药物中的应用 |
CN102552224A (zh) * | 2011-12-16 | 2012-07-11 | 西安交通大学 | 姜黄素衍生物c2在抗结肠癌药物中的应用 |
CN114133372B (zh) * | 2021-10-26 | 2023-11-07 | 广州中大南沙科技创新产业园有限公司 | 一种多芳乙烯β-二酮类化合物或其药学上可接受的盐及其应用 |
-
2008
- 2008-06-05 CN CN 200810071178 patent/CN101434524B/zh not_active Expired - Fee Related
Non-Patent Citations (3)
Title |
---|
Medicinal Chemistry》.2008,第16卷(第6期),第2894–2902页. * |
Satyendra Mishra等人.Synthesis and exploration of novel curcumin analogues as anti-malarial agents.《Bioorganic & Medicinal Chemistry》.2008,第16卷(第6期),第2894–2902页. |
Satyendra Mishra等人.Synthesis and exploration of novel curcumin analogues as anti-malarial agents.《Bioorganic & * |
Also Published As
Publication number | Publication date |
---|---|
CN101434524A (zh) | 2009-05-20 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
KR20190120331A (ko) | Sik 억제제로서의 피리미도피리미디논의 용도 | |
KR101421140B1 (ko) | 메킬리아 락톤 유도체, 그 약제학적 조성물 및 그 제조방법과 용도 | |
CN102234259B (zh) | 含笑内酯衍生物,其药物组合物及其制备方法和用途 | |
CN103946231B (zh) | 齐墩果酸酰胺化衍生物、及其制备方法和应用 | |
CN101434600B (zh) | 姜黄素哌啶酮结构类似物及其用于制备抗肿瘤药物的应用 | |
CN102702298B (zh) | 一种甘草次酸衍生物、其制备方法及医药用途 | |
CN104151391B (zh) | 一种具有抗肿瘤作用的齐墩果酸衍生物及其制备方法和用途 | |
CN101434524B (zh) | 4-(4-羟基-3-甲氧基苯亚甲基)姜黄素及其制备方法和在制备抗癌药物的应用 | |
CN101434525B (zh) | 4-(4-羟基-3-甲氧基苯甲基)姜黄素及其用于制备抗肿瘤药物的应用 | |
CN103097368B (zh) | 用于治疗癌症的三环内酯 | |
CN102153508B (zh) | 3,5-(e)-二亚苄基-n-环丙基哌啶-4-酮及其在制备治疗抗肿瘤药物中的应用 | |
CN114057778A (zh) | 基于二甲基吡啶胺-锌的高抗癌活性配合物及其衍生物和制备方法 | |
CN106083704A (zh) | 3,5‑(E)‑ 二芳亚甲基‑N‑环丙基哌啶‑4‑酮类化合物作为Hsp90抑制剂的应用 | |
CN101691353A (zh) | N-Boc-3,5-(E)-二芳基亚甲基-4-哌啶酮及其在制备治疗抗肿瘤药物中的应用 | |
CN102503888A (zh) | 2-芳基-1,3-异喹啉二酮类抗肿瘤化合物及其合成方法和用途 | |
CN103130632B (zh) | 1-取代苯亚甲基-2-萘酮类衍生物及制备方法和用途 | |
CN109897022B (zh) | 含笑内酯衍生物、其药物组合物及其制备方法和用途 | |
CN102924450A (zh) | 6-(5-吡啶基)-1,2,4-***并吡啶类化合物及其制备方法和用途 | |
CN104592182A (zh) | 一种咖啡酸苯乙酯类化合物及其制备方法及应用 | |
JP5343129B2 (ja) | 水に対する溶解度が改善された新規のシンナムアルデヒド誘導体、その製造方法、それを含む抗癌剤組成物およびそれを用いた癌治療方法 | |
KR101690665B1 (ko) | 신규한 2-하이드록시 커큐미노이드 유도체, 이의 제조 방법 및 이를 포함하는 항암제 조성물 | |
CN113004268B (zh) | 一种抑制肿瘤细胞生长的噻唑化合物及其用途 | |
CN104003998A (zh) | 冬凌草甲素14-o-取代氮芥衍生物、制备方法及用途 | |
CN110407850A (zh) | (5r)-5-羟基雷公藤内酯醇衍生物及其制备方法和应用 | |
CN112979638B (zh) | 一种噻唑化合物及其用途 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
CF01 | Termination of patent right due to non-payment of annual fee | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20120725 |