CN102603805A - 具有抗肿瘤活性的铂（ii）配合物及其制备方法 - Google Patents
具有抗肿瘤活性的铂（ii）配合物及其制备方法 Download PDFInfo
- Publication number
- CN102603805A CN102603805A CN2012100330765A CN201210033076A CN102603805A CN 102603805 A CN102603805 A CN 102603805A CN 2012100330765 A CN2012100330765 A CN 2012100330765A CN 201210033076 A CN201210033076 A CN 201210033076A CN 102603805 A CN102603805 A CN 102603805A
- Authority
- CN
- China
- Prior art keywords
- platinum
- complex
- preparation
- gallic acid
- ring
- 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.)
- Pending
Links
- HRGDZIGMBDGFTC-UHFFFAOYSA-N platinum(2+) Chemical compound [Pt+2] HRGDZIGMBDGFTC-UHFFFAOYSA-N 0.000 title claims abstract description 13
- 238000002360 preparation method Methods 0.000 title claims description 8
- 230000000118 anti-neoplastic effect Effects 0.000 title abstract 3
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims abstract description 63
- 229910052697 platinum Inorganic materials 0.000 claims abstract description 33
- 229940074391 gallic acid Drugs 0.000 claims abstract description 11
- 239000000126 substance Substances 0.000 claims abstract description 8
- LNTHITQWFMADLM-UHFFFAOYSA-N gallic acid Chemical compound OC(=O)C1=CC(O)=C(O)C(O)=C1 LNTHITQWFMADLM-UHFFFAOYSA-N 0.000 claims description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 15
- 235000004515 gallic acid Nutrition 0.000 claims description 10
- 230000000259 anti-tumor effect Effects 0.000 claims description 8
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 4
- 230000000887 hydrating effect Effects 0.000 claims description 4
- 229910001961 silver nitrate Inorganic materials 0.000 claims description 4
- 239000002246 antineoplastic agent Substances 0.000 claims description 2
- 229940041181 antineoplastic drug Drugs 0.000 claims description 2
- 239000002994 raw material Substances 0.000 claims description 2
- FZHLWVUAICIIPW-UHFFFAOYSA-M sodium gallate Chemical compound [Na+].OC1=CC(C([O-])=O)=CC(O)=C1O FZHLWVUAICIIPW-UHFFFAOYSA-M 0.000 claims description 2
- 206010028980 Neoplasm Diseases 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 4
- 239000008213 purified water Substances 0.000 description 4
- 238000005303 weighing Methods 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 230000000452 restraining effect Effects 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 206010034133 Pathogen resistance Diseases 0.000 description 2
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 208000019838 Blood disease Diseases 0.000 description 1
- 206010065553 Bone marrow failure Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 241000675108 Citrus tangerina Species 0.000 description 1
- 241000186227 Corynebacterium diphtheriae Species 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 241000588652 Neisseria gonorrhoeae Species 0.000 description 1
- 235000014676 Phragmites communis Nutrition 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 description 1
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 description 1
- 241000192023 Sarcina Species 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 244000044283 Toxicodendron succedaneum Species 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 229930008399 cantharidic acid Natural products 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 190000008236 carboplatin Chemical compound 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- OFPUVEGIGZQSSD-UHFFFAOYSA-N diethyl-[2-oxo-2-(3-phenylmethoxyanilino)ethyl]azanium;chloride Chemical compound [Cl-].CC[NH+](CC)CC(=O)NC1=CC=CC(OCC=2C=CC=CC=2)=C1 OFPUVEGIGZQSSD-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000005684 electric field Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 208000018706 hematopoietic system disease Diseases 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 201000002037 lung adenoma Diseases 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- ZZDBMDNRQQDSKG-UHFFFAOYSA-N methyl 5-bromo-1-benzofuran-2-carboxylate Chemical compound BrC1=CC=C2OC(C(=O)OC)=CC2=C1 ZZDBMDNRQQDSKG-UHFFFAOYSA-N 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 1
- 229960001756 oxaliplatin Drugs 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 229960001285 quercetin Drugs 0.000 description 1
- 235000005875 quercetin Nutrition 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
本发明的铂配合物中文化学名称为顺式-没食子酸根-(1R，2R)-1，2-环己二胺合铂(II)，分子式为Pt(C6H14N2)(C7H4O5)，分子量为477。该化合物具有良好的抗肿瘤活性。结构如下。
Description
技术领域
本发明涉及医药技术领域，特别是涉及一种具有抗肿瘤活性的新型铂配合物。
背景技术
癌症是一种严重威胁人类健康和生命的疾病，是继心脑血管疾病之后的全球第二大死亡疾病。近年来，由于环境恶化、不良生活习惯及人口老龄化等因素的影响，我国的癌症发病率不断增加。癌症已成为人类亟待攻克的医学难题之一。
在20世纪60年代，美国密执安州立大学教授Rosenberg在研究直流电场对大肠杆菌生长的影响时发现顺铂具有抗癌活性，并通过临床验证，顺铂对多种肿瘤均有良好的治疗效果，从而开辟了金属铂络合物抗癌作用研究的新领域。目前铂类抗癌药物已成为癌症化疗中不可缺少的药物，已有顺铂、卡铂、奥沙利铂、奈达铂、舒铂、洛铂等获批准上市。但目前上市的药物也存在许多自身固有的缺点：毒副作用大，会导致恶心、呕吐、骨髓抑制等，彼此之间存在交叉耐药性及抗癌谱窄等，这些缺点限制了它们更广泛的使用。寻找低毒、高效、广谱及缺乏交叉耐药性成为了铂族药物研究的重要方向。
研究发现，某些天然药物中的有效成分的金属配合物的生物活性明显强于单一的有效成分，以斑蝥酸、槲皮素为离去基团与铂配位的新型抗癌药物相继推出。
没食子酸亦称五倍子酸或桔酸，是一种有机酸，可见于五倍子、漆树、茶 等植物中，化学式C6H2(OH)3COOH。体外对金黄色葡萄球菌、八叠球菌、α-型键球菌、奈瑟氏球菌、绿脓杆菌、弗氏痢疾杆菌、伤寒杆菌Hd、副伤寒杆菌A等有抑制作用，其抑菌浓度为5mg/ml。体外，在3％的浓度下对17种真菌有抑菌作用，对流感病毒亦有一定抑制作用。对吗啉加亚硝钠所致的小鼠肺腺瘤有强抑制作用。本发明根据没食子酸的这个特点，将其与铂配位。
发明内容
本发明的目的是提供一种具有抗肿瘤活性的铂配合物。
本发明的另一目的是提供所述铂配合物的制备方法。
本发明目的所说的铂配合物，以没食子酸根为离去基团，以(1R，2R)-1，2-环己二胺为伴随基团。结构如下：
本发明的铂配合物中文化学名称为顺式-没食子酸根-(1R，2R)-1，2-环己二胺合铂(II)，分子式为Pt(C6H14N2)(C7H4O5)，分子量为477。
本发明的抗肿瘤活性的铂(II)配合物的制备方法如下：
(1)以顺式-二碘-(1R，2R)-1，2-环己二胺合铂(II)(环铂)为起始原料，与硝酸银按物质的量比为1∶2，在50～60℃下反应3～5h；
(2)环铂与没食子酸的物质的量之比为1∶1～1.2，没食子酸与氢氧化钠的物质的量比为1∶1，没食子酸钠与环铂水解溶液反应的pH值约为6～7之间，室温下反应3～5h。
具体实施方式
下面通过实施例来进一步说明本发明。应该正确理解的是：本发明的实施 例中的方法仅仅是用于说明本发明，而不是对本发明的限制。
本发明铂配合物制备：所用试剂：市售纯度不小于98％的顺式-二碘-(1R，2R)-1，2-环己二胺合铂(II)(环铂)，市售分析纯硝酸银，市售分析纯没食子酸，市售分析纯氢氧化钠。
制备过程：称取5.7g(0.01mmol)环铂加入少量纯化水搅成悬浊液，称取3.4g(0.02mmol)硝酸银用纯化水溶解后加入到环铂悬浊液中，补充纯化水到约100ml在55～60℃反应约3.5h，将AgI过滤后得到浅黄色环铂水解溶液。称取1.7g(0.01mmol)没食子酸，加入少量纯化水搅成悬浊液，称取0.4g(0.01mmol)氢氧化钠溶解后加入到没食子酸悬浊液中搅拌至固体完全溶解，将得到的溶液在避光搅拌条件下加入到环铂水解溶液中，用氢氧化钠溶液调节pH6～7之间，在室温下反应约3h，将得到的固体过滤，先后用水、无水乙醇各洗2次后干燥得到2.7g浅黄色固体。元素分析：分子式PtC13H18N2O5，C、H、N、Pt的计算值分别C 32.70％，H 3.77％，N 5.87％，Pt 40.88％；实际检测值C 32.48％，H 3.81％，N5.53％，Pt 41.12％。主要红外峰及归属：O-H(3424.10cm-1st)，N-H(3200.00，1586.00cm-1st)，C-H(2936.00cm-1，2856.23cm-1st)，C＝O(1601.00cm-1st)C＝O(1388.35cm-1δ)FAB+-MS(m/z)：478([M+1]+，100％)。
接种细胞：用含10％胎牛血清的培养液(DMEM或者RMPI1640)配成单个细胞悬液，以每孔5000-10000个细胞接种到96孔板，每孔体积100μl，贴壁细胞提前12小时接种培养。加入待测化合物溶液(固定浓度40μM初筛，在该浓度对肿瘤细胞生长抑制在50％附近的化合物设5个浓度进入梯度复筛)，每孔终体积200μl，每种处理均设3个复孔。显色：37摄氏度培养48小时后，每孔加MTT溶液20μl。继续孵育4小时，终止培养，吸弃孔内培养上清液，每孔加200μl的SDS溶液(10％)，过夜孵育(温度37℃)，使结晶物充分融解。比色：选择 595nm波长，酶联免疫检测仪(Bio-Rad 680)读取各孔光吸收值，记录结果，以浓度为横坐标，细胞存活率为纵坐标绘制细胞生长曲线，应用两点法(Reed and Muench法)计算化合物的IC50(μm)值。
结果见下表：
从结果可以看出，化合物具有一定的体外肿瘤生长抑制活性，对白血病HL-60，肺癌A-549，乳腺癌MCF-7的IC50＜10μm。
Claims (3)
1.一种具有抗肿瘤活性的铂(II)配合物，化学名为顺式-没食子酸根-(1R，2R)-1，2-环己二胺合铂(II)，分子式为Pt(C6H14N2)(C7H4O5)，分子量为477，其结构式为：
2.一种具有抗肿瘤活性的铂(II)配合物的制备方法，其特征在于：
(1)以顺式-二碘-(1R，2R)-1，2-环己二胺合铂(II)(环铂)为起始原料，与硝酸银按物质的量比为1∶2，在50～60℃下反应3～5h；
(2)环铂与没食子酸的物质的量之比为1∶1～1.2，没食子酸与氢氧化钠的物质的量比为1∶1，没食子酸钠与环铂水解溶液反应的pH值约为6～7之间，室温下反应3～5h。
3.权利要求1的铂(II)配合物在制备抗肿瘤药物中的应用。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012100330765A CN102603805A (zh) | 2012-02-14 | 2012-02-14 | 具有抗肿瘤活性的铂（ii）配合物及其制备方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012100330765A CN102603805A (zh) | 2012-02-14 | 2012-02-14 | 具有抗肿瘤活性的铂（ii）配合物及其制备方法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102603805A true CN102603805A (zh) | 2012-07-25 |
Family
ID=46521628
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012100330765A Pending CN102603805A (zh) | 2012-02-14 | 2012-02-14 | 具有抗肿瘤活性的铂（ii）配合物及其制备方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102603805A (zh) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107827934A (zh) * | 2017-11-23 | 2018-03-23 | 台州泰捷化工科技有限公司 | 具有抗癌活性的四价铂配合物、制备方法及应用 |
| CN107955042A (zh) * | 2017-11-23 | 2018-04-24 | 台州泰捷化工科技有限公司 | 具有抗癌活性的铂类配合物、制备方法及应用 |
| CN111973754A (zh) * | 2019-05-21 | 2020-11-24 | 杭州磐田生物技术有限公司 | 含药物纳米颗粒及其制备方法和应用 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4680308A (en) * | 1985-12-26 | 1987-07-14 | Andrulis Research Corporation | Stable soluble 1,2-diaminocyclohexane platinum complexes |
| CN1557822A (zh) * | 2004-02-11 | 2004-12-29 | 昆明贵金属研究所 | 具有抗肿瘤活性的铂配合物 |
| CN1683379A (zh) * | 2005-02-22 | 2005-10-19 | 昆明贵金属研究所 | 新型脂溶性铂(ⅱ)抗肿瘤配合物 |
| CN1923837A (zh) * | 2006-09-29 | 2007-03-07 | 昆明贵研药业有限公司 | 亲脂性铂类抗肿瘤配合物 |
-
2012
- 2012-02-14 CN CN2012100330765A patent/CN102603805A/zh active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4680308A (en) * | 1985-12-26 | 1987-07-14 | Andrulis Research Corporation | Stable soluble 1,2-diaminocyclohexane platinum complexes |
| CN1557822A (zh) * | 2004-02-11 | 2004-12-29 | 昆明贵金属研究所 | 具有抗肿瘤活性的铂配合物 |
| CN1683379A (zh) * | 2005-02-22 | 2005-10-19 | 昆明贵金属研究所 | 新型脂溶性铂(ⅱ)抗肿瘤配合物 |
| CN1923837A (zh) * | 2006-09-29 | 2007-03-07 | 昆明贵研药业有限公司 | 亲脂性铂类抗肿瘤配合物 |
Non-Patent Citations (3)
| Title |
|---|
| QING-SONG YE等,: "Synthesis and in vitro cytotoxicity of novel lipophilic (diamine)platinum(II) complexes of salicylate derivatives", 《BIOORGANIC & MEDICINAL CHEMISTRY LETTERS》 * |
| YAO YU等,: "Synthesis and anticancer activity of lipophilic platinum(II) complexes of 3,5-diisopropylsalicylate", 《EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY》 * |
| 李沐涵等,: "没食子酸抗肿瘤作用研究进展", 《中医药信息》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107827934A (zh) * | 2017-11-23 | 2018-03-23 | 台州泰捷化工科技有限公司 | 具有抗癌活性的四价铂配合物、制备方法及应用 |
| CN107955042A (zh) * | 2017-11-23 | 2018-04-24 | 台州泰捷化工科技有限公司 | 具有抗癌活性的铂类配合物、制备方法及应用 |
| CN107955042B (zh) * | 2017-11-23 | 2020-01-21 | 青岛大学附属医院 | 具有抗癌活性的铂类配合物、制备方法及应用 |
| CN107827934B (zh) * | 2017-11-23 | 2020-05-08 | 朱瑞国 | 具有抗癌活性的四价铂配合物、制备方法及应用 |
| CN111973754A (zh) * | 2019-05-21 | 2020-11-24 | 杭州磐田生物技术有限公司 | 含药物纳米颗粒及其制备方法和应用 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Prencipe et al. | Silver (I) n-heterocyclic carbene complexes: A winning and broad spectrum of antimicrobial properties | |
| Ediyilyam et al. | Synthesis, characterization and physicochemical properties of biogenic silver nanoparticle-encapsulated chitosan bionanocomposites | |
| Abbasi et al. | Exploring physical characterization and different bio-applications of elaeagnus angustifolia orchestrated nickel oxide nanoparticles | |
| Matsia et al. | Chromium flavonoid complexation in an antioxidant capacity role | |
| CN105566353A (zh) | 一种化合物及其制备方法 | |
| Milenković et al. | Synthesis, characterization and biological activity of three square-planar complexes of Ni (II) with ethyl (2E)-2-[2-(diphenylphosphino) benzylidene] hydrazinecarboxylate and monodentate pseudohalides | |
| Kiani et al. | Comparative evaluation of biomedical applications of zinc nanoparticles synthesized by using Withania somnifera plant extracts | |
| CN102603805A (zh) | 具有抗肿瘤活性的铂（ii）配合物及其制备方法 | |
| Ugalde-Arbizu et al. | Dual anticancer and antibacterial properties of silica-based theranostic nanomaterials functionalized with coumarin343, folic acid and a cytotoxic organotin (IV) metallodrug | |
| Ugalde-Arbizu et al. | Antibacterial properties of mesoporous silica nanoparticles modified with fluoroquinolones and copper or silver species | |
| Savino et al. | Multi-Acting Mitochondria-Targeted Platinum (IV) Prodrugs of Kiteplatin with α-Lipoic Acid in the Axial Positions | |
| Mokesch et al. | Fine-tuning the activation mode of an 1, 3-indandione-based ruthenium (ii)-cymene half-sandwich complex by variation of its leaving group | |
| CN101130556A (zh) | 抗癌环己二胺金属配合物 | |
| CN102659849B (zh) | 一种具有抗肿瘤活性的铂（ii）配合物及其制备方法 | |
| Petrov et al. | Chromatographic profile and redox-modulating capacity of methanol extract from seeds of Ginkgo biloba L. originating from plovdiv region in Bulgaria | |
| Santra et al. | A study on the formation of the nitro radical anion by ornidazole and its significant decrease in a structurally characterized binuclear Cu (II)-complex: impact in biology | |
| Kikionis et al. | Development of Novel Pharmaceutical Forms of the Marine Bioactive Pigment Echinochrome A Enabling Alternative Routes of Administration | |
| CN111909059B (zh) | 具有抑菌效果的Cu-二甲双胍配合物、其晶体结构以及制备方法和应用 | |
| CN105748358B (zh) | 一种沉香精华赋活水及其制备方法 | |
| Golubeva et al. | Synthesis and study of zeolites modified by silver nanoparticles and clusters: biological activity | |
| Velcheva et al. | Platinum (IV) complexes of the 1, 3, 5-triamino analogue of the biomolecule cis-inositol designed as innovative antineoplastic drug candidates | |
| CN105670998A (zh) | 一种钙化癌细胞的方法 | |
| Ivanova et al. | New Iron (III)-Containing Composite of Salinomycinic Acid with Antitumor Activity—Synthesis and Characterization | |
| Corredoira-Vázquez et al. | Dy4, Dy5, and Ho2 Complexes of an N3O2 Aminophenol Donor: A Dy5-µ3-Peroxide Single Molecule Magnet | |
| WO1999018083A1 (en) | N,n'-(sulphonyldi-1, 4-phenylen) bis (n'',n''- dimethylformamidin)-1, 2,3,4-tetrahydro- 6-methyl-2, 4-dioxo-5-pyrimidinsulphonate for stimulating cellular metabolism and having an immunotropic and anti-bacterial activity and method for producing the same |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20120725 |